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      • id1398
      • user_id81
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      • abstract_of_study<p>\n The Severe Malaria Africa – A Consortium for Research and Trials (SMAART) aims to significantly improve outcomes for severe malaria through enhanced and accelerated research initiatives. SMAART serves as an efficient operational platform for coordinating future research, enabling continuous updates to disease definitions and treatment guidelines based on the latest evidence. During its 2-day inception meeting, SMAART assembled a multidisciplinary team including scientists from major Wellcome Trust programs (KEMRI in Kenya, Malawi-Liverpool-Wellcome Trust Unit in Malawi, Mahidol Oxford Tropical Medicine Research Unit in Thailand), clinical trial experts (MRC CTU at UCL), and African clinician scientists from multiple countries.</p>\n<p>\n The meeting focused on establishing the current burden of severe malaria through literature review, updating our understanding of the disease's clinical spectrum, identifying accurate diagnostic tools, and setting best practices to address research gaps. Key discussions revolved around refining practice guidelines in response to challenges like artemisinin resistance and persistently high mortality rates despite effective antimalarial treatments. The meeting also laid out plans for future clinical trials, emphasizing pathophysiological research and innovative trial methodologies.</p>\n<p>\n Despite various supportive therapies being explored through ongoing and planned clinical trials, the evidence remains sparse, underlining the urgent need for more comprehensive studies. The consortium stressed the necessity of an adaptive trial platform to properly evaluate potential beneficial adjunctive therapies and identified high-priority risk factors and interventions for a Phase II platform trial aimed at improving short and long-term outcomes.</p>\n<p>\n This structured approach aims to address severe malaria with targeted treatments and innovative research methodologies, with each intervention's background, justification, and rationale detailed in specific appendix protocols.</p>\n
      • study_title<div>\n Severe Malaria A Research and Trials consortium - Multisite Adaptive Platform trial</div>\n
      • laymans_summary<div>\n Children with severe malaria come to hospital very sick and need urgent care. Despite the introduction of the malaria vaccine in some areas of Africa and increased bednet use, severe malaria is still causing child deaths and hospitalisations. Even on the best anti-malarial treatments many African children with severe malaria have poor outcomes with including deaths which tend to occur on the first day of arrival to hospital. One of the bad things that happen in severe malaria is that red blood cells that are infected with malaria parasites stick to the very deep parts of our blood vessels. This occurs throughout the body and affects vital places such as the brain or kidneys. Thus, children come to hospital with different symptoms such as in a coma or with fits or with anaemia. They will be treated immediately with anti-malarials and may also receive antibiotics. Other treatments targeted at symptoms or specific areas of the body may also help them recover (called adjunctive therapy).</div>\n<div>\n The World Health Organisation has developed guidelines for treatment of severe malaria but much of the information used to develop the recommendations on adjunctive therapy are based on expert opinion and not data from clinical trials and studies which are a better source of evidence. The SMAART-MAP trial aims to identify adjunctive therapies that will help children with severe malaria get better faster in the short term (within 3 days of coming to hospital) and that could then be studied further in larger numbers to see if they are able to reduce the number of children who die or return to hospital.</div>\n<div>\n The trial has been designed to look at the impact of these adjunctive therapies on different symptoms or body areas. In the trial these different areas are called ‘domains’. One adjunctive therapy will be investigated within each domain of the trial. It is called an adaptive trial as new domains can be added to the structure of the trial after it has started, and all domains have some joint processes and will be run by the same staff. This document is the master protocol which outlines those joint processes and explains the main objective of the trial. Appendices describe the adjunctive therapies within each domain in more detail.</div>\n<div>\n A computer programme will assign a child to receive either the adjunctive treatment or the standard of care at that site within a domain at random (like the flip of a coin). Each child can only be enrolled to one domain and thus possibly receive one adjunctive treatment through the trial. Each child will be monitored through bedside observations and depending on the domain they may need some additional tests. This information will help us compare how children receiving the adjunctive therapy and receiving standard of care are responding to their treatment.</div>\n
      • short_titleSMAART-MAP trial
      • protocol_noECCT/24/04/03
      • version_no1.02
      • date_of_protocol09-02-2024
      • study_drugSMAART_MAP Trial_(Levetiracetam,Paracetamol and Blood products\' (whole blood and Package Cells)
      • disease_conditionSevere Malaria
      • product_type_biologicals1
      • product_type_proteins1
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
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      • product_type_medical_device0
      • product_type_chemical_nameParacetamol and Levetiracetam
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressCGMRCCSC@kemri-wellcome.org
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      • declaration_applicantEmmanuel Oguda
      • declaration_date107-08-2024
      • declaration_principal_investigatorProf.Kathryn Maitland
      • declaration_date207-08-2024
      • placebo_presentNo
      • study_objectives<p>\n The SMAART-MAP trial aims to identify promising adjunctive therapies for advancement into a comprehensive Phase III trial focused on severe malaria with an emphasis on mortality outcomes. Utilizing an adaptive platform design, the trial is structured to incorporate multiple domains, enabling the evaluation of various adjunctive therapies across diverse clinical manifestations of severe malaria efficiently.</p>\n<p>\n <strong>Primary Objective</strong></p>\n<ul>\n <li>\n The primary objective is to evaluate the therapeutic efficacy of each intervention within its respective domain. This evaluation will utilize early indicators such as biomarkers or clinical assessments conducted within 24-72 hours post-intervention.</li>\n</ul>\n<p>\n <strong>Secondary Objectives</strong></p>\n<ul>\n <li>\n To determine the impact of the interventions on clinical outcomes, including readmission rates and mortality, assessed at 28 days and 90 days following randomization.</li>\n <li>\n To evaluate the incidence and severity of Grade 3 or 4 adverse events, as well as any adverse events associated with the interventions or their comparators.</li>\n <li>\n To explore the effects of defined severe malaria criteria, specifically platelet counts ≤150,000/μL and plasma pfHRP2 concentrations ≥800 ng/mL, on the differentiation between randomized groups.</li>\n <li>\n In a sub study, to assess the performance characteristics of a point-of-care (POC) pfHRP2 test in comparison with quantitative plasma pfHRP2 measurements.</li>\n</ul>\n<p>\n These objectives are designed to guide the systematic exploration and evaluation of adjunctive therapies in the treatment of severe malaria, thereby contributing to improved treatment strategies and outcomes.</p>\n
      • principal_inclusion_criteria<p>\n Eligibility criteria for SMAART-MAP (all domains)</p>\n<ol>\n <li>\n Aged >3 months and <12 years</li>\n <li>\n Admitted to the paediatric ward in the last 24 hours at screening</li>\n <li>\n Current or recent evidence of malaria (slide or rapid diagnostic test (RDT) positive in this admission)</li>\n <li>\n Guardian willing to provide consent</li>\n</ol>\n<div>\n <strong>Additional domain-specific inclusion criteria.</strong></div>\n<div>\n <div>\n Severe Anaemia Domain</div>\n <ol>\n <li>\n Hb <6g/dl</li>\n <li>\n One or more or the following severity signs: Hb<4g/dl, prostration, impaired consciousness, respiratory distress, history of passing red or coca-coloured urine in this illness</li>\n </ol>\n</div>\n<p>\n Cerebral Malaria Domain (EITHER)</p>\n<ol>\n <li>\n One or more reported seizures in the current episode of illness and altered consciousness (BCS≤4) at screening OR</li>\n <li>\n Presence of coma (BCS ≤2) at screening regardless of history.</li>\n</ol>\n<p>\n Renal function Domain</p>\n<ol>\n <li>\n Creatinine >1.5xULN on point-of-care assay or laboratory test at screening</li>\n <li>\n Meet one of the current WHO severity criteria (clinical or laboratory (where these tests are done routinely)) (Group 1 and 2 from the recent WHO reclassification of severe malaria)</li>\n</ol>\n
      • principal_exclusion_criteria<p>\n Domains specific exclusion criteria.</p>\n<p>\n <strong>Severe Anaemia Domain</strong></p>\n<ol>\n <li>\n Known congenital or valvular heart disease (not surgically corrected)</li>\n</ol>\n<p>\n <strong>Cerebral Malaria Domain</strong></p>\n<ol>\n <li>\n Received an anticonvulsant within 6 hours of screening or between screening and randomisation.</li>\n <li>\n Known cerebral palsy or significant neuro-development delay.</li>\n</ol>\n<p>\n <strong>Renal function Domain</strong></p>\n<ol>\n <li>\n Received paracetamol within 6 hours of screening or between screening and randomisation</li>\n <li>\n Known allergy to paracetamol</li>\n <li>\n Severe malnutrition (middle upper arm circumference MUAC<11.5cm)</li>\n</ol>\n
      • primary_end_points<p>\n Primary endpoints are specific to each domain which include.</p>\n<p>\n Cerebral Malaria Domain</p>\n<ul>\n <li>\n Number of witnessed seizures sufficient to start or change anticonvulsant medication by 72 hours.</li>\n</ul>\n<p>\n Renal Function Domain</p>\n<ul>\n <li>\n Area Under the Curve (AUC) for creatinine over the first 72 hours from randomization based on measurements assayed retrospectively on stored plasma samples taken at randomisation (treated as time 0/baseline) at 24, 48, and 72 hours.</li>\n</ul>\n<p>\n Severe Anaemia Domain:</p>\n<ul>\n <li>\n Change in haemoglobin at 24 hours (adjusted for baseline)</li>\n</ul>\n<p>\n <strong>Secondary endpoints</strong></p>\n<p>\n These will encompass all domains and will include.</p>\n<ul>\n <li>\n Readmissions and mortality to day 28 and day 90.</li>\n <li>\n Grade 3 or 4 adverse events (AEs); and AEs judged related to domain-specific interventions or their comparators during admission as detailed in the domain-specific appendices.</li>\n</ul>\n
      • scope_diagnosis0
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      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
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      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory1
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<div>\n <strong>Kilifi_Kenya</strong></div>\n<div>\n  </div>\n<div>\n We will draw study clinicians and nurses from the staff currently working in the KEMRI HDU Research Unit, and they will be trained on all aspects of the study protocol and procedures. Additionally, a dedicated study clinician and nurse will closely assist in the operation of the study activities within the trial unit (HDU).</div>\n<p>\n Trial Coordinator: Emmanuel Oguda</p>\n<p>\n The trial will be coordinated and conducted in the KEMRI High Dependency Unit, as well as in other designated pediatric units across various participating sites located in seven hospitals in Africa.</p>\n<p>\n Chief Principal Investigator: Professor Kathryn Maitland will oversee the trial overall.</p>\n<p>\n Local Principal Investigator: Professor Mainga Hamaluba will be responsible for local oversight.</p>\n<p>\n Each site will be overseen and evaluated by specific Country Principal Investigators (PIs) as listed below:</p>\n<p>\n <strong>Democratic Republic of the Congo</strong></p>\n<p>\n Université de Kinshasa, Campus UNIKIN, Lemba, BP 11850, Kinshasa, DRC</p>\n<p>\n Principal Investigator: Prof Marie Onyamboko, MD, DPhil</p>\n<p>\n Co-Investigator: Dr. Catarina Fanello, PhD</p>\n<p>\n <strong>Uganda</strong></p>\n<p>\n Country Principal Investigator: Prof. Peter Olupot Olupot</p>\n<p>\n <strong>Soroti Regional Hospital</strong></p>\n<p>\n Co-Investigator: Dr. Florence Aloroker, MBChB, MMed</p>\n<p>\n Study Site Coordinator: Denis Amorut, BsHSM, RCN</p>\n<p>\n <strong>Dr. Ambrosoli Hospital, Kalongo</strong></p>\n<p>\n Site Investigator: Dr. Okao Maurice, MD, MMED Pediatrics</p>\n<p>\n Study Site Coordinator: Dr. Modester Akite, MD</p>\n<p>\n <strong>Zambia</strong></p>\n<p>\n St. Paul's Mission Hospital, Nchelenge, Luapula Province</p>\n<p>\n Tropical Diseases Research Centre, Ndola Teaching Hospital, P.O Box 71769, Ndola</p>\n<p>\n Principal Investigator: Dr. Mike Chaponda, MSc, MBChB, MSc, DTMH</p>\n<p>\n Co-Investigators: Dr. Sam Miti, MBChB, MMed; Dr. Jonathan Gwasupika, MBChB</p>\n<p>\n <strong>Ghana</strong></p>\n<p>\n Komfo Anokye Teaching Hospital, Bantama High Street, P.O Box 1934, Kumasi</p>\n<p>\n Department of Child Health, Kwame Nkrumah University of Science and Technology, Kumasi</p>\n<p>\n Principal Investigator: Professor Daniel Ansong, MBChB, MSc</p>\n<p>\n Co-Investigators: Prof. Tsiri Agbenyega, PhD; Dr. Justice Sylverken, MBChB</p>\n<p>\n <strong>Mozambique</strong></p>\n<p>\n Hospital Central de Quelimane, Av. Julius Nyerere, Estrada Regional Numero 470, Bairro Namuinho</p>\n<p>\n Manhiça Health Research Centre (CISM), P.O BOX 1929, Manhiça</p>\n<p>\n Co-Lead Investigators: Dr. Rosauro Varo, MD, MSc, PhD, Pediatrician; Dr. Pedro Aide, MD, MSc, PhD</p>\n<p>\n Co-Investigator: Dr. David Torres, MD, MSc, Pediatrician</p>\n<p>\n Co-Investigator: Professor Quique Bassat, MD, MSc, PhD</p>\n
      • other_details_explanation<p>\n The SMAART-MAP trial is being conducted in Kenya, among other African countries, to study hospitalized children with severe malaria, leveraging local hospitals to investigate potential treatments and interventions in a real-world setting where malaria prevalence is high. This facilitates direct evaluation of medical strategies in environments most affected by the disease, aiming to improve patient outcomes and inform future healthcare practices in similar regions.</p>\n
      • other_details_regulatory_notapproved<ol>\n <li>\n Zambia Medicine Regulatory Authority_(ZAMRA)_Zambia</li>\n <li>\n Food and Drugs Authority (FDA) _Ghana</li>\n <li>\n National Medicines Regulatory Authority (Autoridade Nacional Reguladora de Medicamentos, ANARME) _Mozambique</li>\n <li>\n Comité d'Ethique de la Recherche ECOLE DE SANTÉ PUBLIQUE DE KINSHASA</li>\n <li>\n UNIVERSITE DE KINSHASA_Democratic Republic of Congo</li>\n <li>\n National Drug Authority _NDA (Uganda)</li>\n</ol>\n
      • other_details_regulatory_approved<p>\n Not Applicable</p>\n
      • other_details_regulatory_rejected<p>\n Not Applicable</p>\n
      • other_details_regulatory_halted<p>\n Not Applicable</p>\n
      • estimated_duration24 months
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorStandard of Care
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKilifi County Hospital
      • single_site_physical_addressP.o Box 230 Kilifi
      • single_site_contact_personEmmanuel Oguda
      • single_site_telephone0748588041
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states6
      • number_of_sites
      • multi_country_listUganda, Zambia, Ghana, Kenya, Democratic Republic of the Congo and Mozambique
      • data_monitoring_committeeYes
      • total_enrolment_per_siteThe minimum number of participants expected per site is 10, while the maximum is 60.
      • total_participants_worldwide450
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerYes
      • population_childrenYes
      • population_adolescentNo
      • population_above_18No
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationYes
      • subjects_incapable_consentYes
      • subjects_specifySick children below the age of 12 years
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameProf Mainga Hamaluba
      • investigator1_middle_name
      • investigator1_family_nameHamaluba
      • investigator1_qualificationMedical Doctor
      • investigator1_professional_addressKilifi Clinical Trials Unit, PO Box 230, Kilifi
      • investigator1_telephone+254 709983946
      • investigator1_emailMHamaluba@kemri-wellcome.org
      • organisations_transferred_Yes
      • number_participantsSince this is a multi-centred trial, the enrollment of study participants will be competitive across the participating sites.
      • notification<p>\n We have uploaded all the relevent document sfor review as per the checklist for submission clinical trials application for approval. </p>\n<h1>\n  </h1>\n
      • approval_date29-08-2024
      • submitted1
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      • deleted_date(null)
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      • date_submitted15-04-2024
      • unsubmitted1
      • initial_date_submitted15-04-2024
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have been reviewed under the AVAREF pathway and approved.
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      • modified2024-08-29 23:35:45
      • created2024-04-15 08:48:11
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        • id1059
        • application_id1398
        • given_nameProf Kathryn Maitland
        • middle_name
        • family_nameMaitland
        • qualificationProfessor of Paediatric Tropical Infectious Diseases (MBBS PhD)
        • professional_addressBOX 230 KILIFI
        • telephone+254733411022
        • emailkathryn.maitland@gmail.com
        • created2024-04-15 09:41:34
        • modified2024-08-07 16:24:21
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        • created2024-04-15 09:41:34
        • modified2024-08-07 16:24:21
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    • Sponsor(array)
      • 0(array)
        • id740
        • application_id1398
        • sponsorImperial College London
        • sponsor_typeOthers
        • contact_personJoint Research Compliance Office
        • addressImperial College London Room 215, Level 2, Medical School Building Norfolk Place London, W2 1PG
        • telephone_numberTel: 020 7594 1872
        • fax_number
        • cell_numberTel: 020 7594 1872
        • email_addressr.nicholson@imperial.ac.uk
        • created2024-04-15 09:41:34
        • modified2024-08-07 16:24:21
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      • id1382
      • user_id613
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      • abstract_of_study<p>\n Shigellosis remains a major public health problem around the world; it is one of the leading causes of diarrheal disease in low- and middle-income countries (LMIC), particularly in young children. The Global Burden of Disease study (IHME) estimated that in 2017 Shigella caused approximately 238,000 deaths globally and, with 15.2%, it ranked second with regard to pathogen contributions in global diarrheal deaths. In infants, in LMIC, particularly where healthcare resources are limited, shigellosis can often lead to death. There is presently no widely available vaccine against Shigella. The candidate vaccine, altSonflex1-2-3, has been evaluated for the FTiH in adults in Belgium, and is currently evaluated in a Phase 2 age de-escalation clinical study in Kenya, with the aim of identifying a preferred dose, using a 3-dose vaccinations schedule in infants from 9 months of age (NCT05073003). The current Phase 2 clinical study will evaluate the immunogenicity and safety of an alternative 2-dose vaccination schedule. The candidate vaccine, altSonflex1-2-3, will be administered intramuscularly by study site staff and contains 15 μg (Dose C), 7.5 μg (Dose B), or 3.75 μg (Dose A) of OAg for each antigen component. About 400 9-month old infants will be screened to enroll 200 participants. The results of this study will allow the selection of the most appropriate dose for further vaccine development in infants 9 months of age, which is the main target age group for this vaccine. The study findings will be shared with all authorities having oversight of this protocol including the sponsor, Kenya Medical Research Institute Scientific Ethics Review Unit, Pharmacy and Poisons Board, Walter Reed Army Institute of Research Institutional Review Board and Kenya’s Ministry of Health.</p>\n
      • study_title<p>\n A Phase 2 single-blind, randomized, controlled, single center study to assess the immunogenicity and safety of a 2-dose schedule with GVGH altSonflex1-2-3 vaccine in African infants (H06_02TP)</p>\n
      • laymans_summary<p>\n Lay Title: A study on the safety and immune responses to the GVGH vaccine against shigellosis in infants</p>\n<p>\n Shigellosis is an infectious disease caused by a group of bacteria called Shigella. Shigellosis remains a major public health problem around the world; it is one of the leading causes of diarrheal disease in low- and middle-income countries (LMIC), particularly in young children. The Global Burden of Disease study (IHME) estimated that in 2017 Shigella caused approximately 238,000 deaths globally. In infants, in LMIC, particularly where healthcare resources are limited, shigellosis can often lead to death. There is presently no widely available vaccine against Shigella. Treatment for shigellosis is mainly supportive to keep patients stable. Shigellosis can be treated with antibiotics but many Shigella bacteria no longer respond well to or are resistant to most of the used antibiotics. Thus, a very important way to fight Shigella is through prevention with the use of vaccination.. The aim of the study is to assess how an experimental Shigella vaccine, called altSonflex1-2-3, given in two doses, makes the body to produce proteins that fight off the bacteria causing shigellosis and to assess the side effects the vaccine may cause. Infants who are 9 months old will receive 2 injections of Shigella vaccine or 2 injections of the control vaccines. The benefits of this study include, participants or participants’ parents may gain medical advice about their own or their children’s health status H06_02TP /WRAIR # /KEMRI/SERU/CCR/0327/4829 Kericho Site Specific Addendum Version 2.0 dated 15 Nov 2023 Page 7 of 30 through the medical evaluations and laboratory assessments associated with the study. Vaccines administered as control and not routinely given will be provided free of charge and can provide protection against Salmonella Typhi, diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and disease caused by Haemophilus influenzae type b. The infants who will be assigned to receive the shigella vaccine will receive THYPIBEV vaccine after the study is completed as a benefit. The results of this study will allow the selection of the most appropriate dose for further vaccine development in infants 9 months of age, which is the main target age group for this vaccine.</p>\n
      • short_titleH06_02TP
      • protocol_noECCT/24/02/08
      • version_no1
      • date_of_protocol19-12-2022
      • study_drugShigella 4-component generalized modules for membrane antigens vaccine (altSonflex1-2-3)
      • disease_conditionShigellosis
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines1
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressKericho.DRS@usamru-k.org
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      • applicant_pictorial_sample1
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      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicant+254 110 122
      • declaration_date127-02-2024
      • declaration_principal_investigatorJOSPHAT KOSGEI
      • declaration_date227-02-2024
      • placebo_presentNo
      • study_objectives<p>\n 1.To evaluate the immunogenicity profile of the altSonflex1-2-3 vaccine (Dose A, Dose B and Dose C) administered at 9 and 15 months using anti-LPS/OAg ELISA</p>\n<p>\n 2. To evaluate the seroresponse of the altSonflex1-2-3 vaccine (Dose A, Dose B and Dose C) administered at 9 and 15 months using anti-LPS/OAg ELISA</p>\n<p>\n 3.T o evaluate the safety and reactogenicity of the altSonflex1-2-3 vaccine (Dose A, Dose B and Dose C) administered at 9 and 15 months.</p>\n<p>\n 4 To evaluate the immunogenicity of co-administered MR-VAC administered at 9 and 15 months.</p>\n<p>\n 5. To evaluate the immunogenicity profile of the altSonflex1-2-3 vaccine (Dose A, Dose B and Dose C) administered at 9 and 15 months by SBA, in a subset of infants.</p>\n<p>\n 6. To evaluate the seroresponse of the altSonflex1-2-3 vaccine (Dose A, Dose B and Dose C) administered at 9 and 15 months by SBA, in a subset of infants.</p>\n<p>\n  </p>\n
      • principal_inclusion_criteria<p>\n Participants are eligible to be included in the study only if all of the following criteria apply:</p>\n<p>\n • Participants’ parent(s)/LAR(s), who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g., completion of the diary cards, return for follow-up visits).</p>\n<p>\n • Written or witnessed/thumb printed informed consent obtained from the parent(s)/LAR(s) of the participant prior to performance of any study specific procedure.</p>\n<p>\n • Healthy participants as established by medical history, clinical examination, and laboratory assessment.</p>\n<p>\n • Participants satisfying all screening requirements.</p>\n<p>\n • Participants seronegative for hepatitis B, and hepatitis C.</p>\n<p>\n • A male or female 9 months of age at the time of the first study intervention administration.</p>\n<p>\n • Normal nutritional (weight-for-length) Z score (-2 standard deviations or greater).</p>\n<p>\n • Previously completed routine childhood vaccinations to the best knowledge of the participant’s parent(s)/LAR(s).</p>\n<p>\n • Born at a gestation period of ≥37 weeks to the best knowledge of the participant’s parent(s)/LAR(s).</p>\n<p>\n • Participants negative for human immunodeficiency virus as confirmed by DNA polymerase chain reaction testing.</p>\n<p>\n • Participants negative for HLA-B27</p>\n
      • principal_exclusion_criteria<p>\n Medical Conditions</p>\n<p>\n •Known exposure to Shigella during lifetime of the participant as confirmed during interview with the participant’s parent(s)/LAR(s) or documented by participant’s records (e.g., history of microbiologically-confirmed Shigella infection).</p>\n<p>\n • Progressive, unstable, or uncontrolled clinical conditions. CONFIDENTIAL 219449 Protocol Final 19 Dec 2022 31</p>\n<p>\n • History (known or suspected) of any reaction or hypersensitivity likely to be exacerbated by any component of the study intervention.</p>\n<p>\n • Major congenital defects, as assessed by the investigator.</p>\n<p>\n • Recurrent history or uncontrolled neurological disorders or seizures.</p>\n<p>\n • Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). • Hypersensitivity (known or suspected), including allergy, to medicinal products, vaccines, or medical equipment whose use is foreseen in this study.</p>\n<p>\n • Clinical conditions representing a contraindication to IM vaccination and blood draws.</p>\n<p>\n • Any behavioral or cognitive impairment or psychiatric disease that, in the opinion of the investigator, may interfere with the participant’s ability to participate in the study.</p>\n<p>\n • Acute disease and/or fever (defined as temperature ≥38.0°C) at the time of enrollment*. *The participant can still be enrolled into the study at a time when the acute disease and/or fever has resolved.</p>\n<p>\n • Any clinically significant* hematological and/or biochemical laboratory abnormality. *The investigator should use his/her clinical judgment to decide which abnormalities are clinically significant.</p>\n<p>\n • Confirmed positive COVID-19 test during the period starting 30 days before the first administration of study interventions (Day -30 to Day 1).</p>\n<p>\n • Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study.</p>\n<p>\n • Acute or chronic clinically significant pulmonary, cardiovascular, hepatic, or renal functional abnormality, as determined by physical examination or laboratory screening tests.</p>\n
      • primary_end_points<p>\n 1. Anti-serotype-specific Shigella LPS/OAg* serum IgG GMCs/GMTs, as measured by ELISA, before each study intervention administration (Day 1 and Day 169), and 28 days after each study intervention administration (Day 29 and Day 197), for each study intervention group.</p>\n<p>\n 2. mber of infants with at least a 4-fold increase in anti-serotypespecific Shigella LPS/OAg* serum IgG, as measured by ELISA, at 28 days after each study intervention administration (Day 29 and Day 197), compared to baseline (Day 1), and compared to pre-administration (Day 1 and Day 169, respectively), for each study intervention group.</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety0
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory1
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n The Kericho CRC is equipped with two emergency rooms with equipment and medications to provide immediate emergency care in the event of emergencies such as anaphylactic reactions and provisions (resuscitation equipment) are in place for immediate resuscitation on site. Additionally, the Kericho site has a standby, fully equipped ambulance for evacuation of participants for more specialized care when necessary. The study staff (clinicians/nurses) are trained on handling emergencies. For inpatient services, participants will be hospitalized at Unilever Tea Kenya (UTK) Central Hospital which is a private company facility owned by the UTK tea company. The site has been using UTK hospital as a satellite site for inpatient admissions of participants requiring inpatient services. The hospital is located about two kilometers from the CRC and has both outpatient and inpatient services.</p>\n
      • other_details_explanation<p>\n The clinical study will be performed in the same center (Kenya Medical Research Institute [“KEMRI”]/ United States Army Medical Research Directorate-Africa/Kenya [MRD-A/K]), where the altSonflex1-2-3 vaccine dose A, B and C have been previously administered in infants 9 months of age with a 3-dose vaccination schedule, in a FTiH Phase 1/2 study (NCT05073003). The Phase 1/2 clinical study included a Phase 1 (FTiH) part, conducted in healthy adults in Belgium; the Phase 2 part is ongoing in Kenya, using an age de-escalation approach, including adults, children and infants, with the primary objectives of identifying the preferred dose of the candidate vaccine among infants and evaluating the safety and reactogenicity of the candidate vaccine among adults, children and infants. The present study will only commence enrollment after all the planned safety reviews by the GSK iSRC and SRT in the Phase 1/2 trial have been completed as per protocol (i.e., after evaluation of data collected up to 7 days after the first study intervention administration in the dose-finding cohort of all infants who were vaccinated in the first 7 weeks of enrollment), and after enrollment has been completed.</p>\n
      • other_details_regulatory_notapproved<p>\n Walter Reed Army IRB</p>\n<p>\n Application submitted 24 Jan 2024.</p>\n
      • other_details_regulatory_approved<p>\n KEMRI SERU</p>\n<p>\n Approval attached dated 24 January 2024.</p>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n None</p>\n
      • estimated_duration2 years
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindYes
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorTYPHIBEV, MR-VAC,
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKEMRI WRP CRC KERICHO
      • single_site_physical_addressOFF HOSPITAL ROAD
      • single_site_contact_personDR JOSPAHT KOSGEI
      • single_site_telephone+254 729 110 122
      • multiple_sites_member_stateNo
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites
      • multi_country_list
      • data_monitoring_committeeYes
      • total_enrolment_per_site200
      • total_participants_worldwide200
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerYes
      • population_childrenNo
      • population_adolescentNo
      • population_above_18No
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsNo
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentYes
      • subjects_specify9-month old infants
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameFredrick
      • investigator1_middle_name
      • investigator1_family_nameSawe
      • investigator1_qualificationMBChB MMED
      • investigator1_professional_addressP O BOX 1357, KERICHO
      • investigator1_telephone+254 703 247 902
      • investigator1_emailFredrick.sawe@usamru-k.org
      • organisations_transferred_No
      • number_participants200
      • notification
      • approval_date31-05-2024
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted28-02-2024
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have been addressed.
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2024-08-12 11:55:50
      • created2024-02-27 08:45:53
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id1042
        • application_id1382
        • given_nameJosphat
        • middle_name
        • family_nameKosgei
        • qualificationMBChB, MSc, DLSHTM
        • professional_addressP O BOX 1357, KERICHO
        • telephone+254 729 110 122
        • emailJosphat.kosgei@usamru-k.org
        • created2024-02-27 09:25:48
        • modified2024-02-28 09:22:51
    • SiteDetail(array)
      • 0(array)
        • id1677
        • application_id1382
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2024-02-27 09:25:48
        • modified2024-02-28 09:22:51
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id727
        • application_id1382
        • sponsorGlaxoSmithKline Biologicals SA
        • sponsor_typeIndustry
        • contact_person
        • addressRue De L\'Institut 89 1330 Rixensart Belgium
        • telephone_number+32 2 656 81 11
        • fax_number
        • cell_number+32 2 656 81 11
        • email_addresspietro.x.ferruzzi@gsk.com
        • created2024-02-27 09:25:48
        • modified2024-02-28 09:22:51
  • 2(array)
    • Application(array)
      • id1379
      • user_id622
      • trial_status_id(null)
      • abstract_of_study<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>Protocol Number: CO44194</strong></p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>Study Name: TNBC</strong></p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>Version Number: 4</strong></p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>Test Compound: </strong> <b><span style=\"font-family: Arial, Helvetica, sans-serif; font-size: small; color: rgb(34, 34, 34);\">Tobemstomig (</span><span style=\"font-family: Arial, Helvetica, sans-serif; font-size: small; color: rgb(34, 34, 34);\">RO7247669)</span></b></p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>STUDY RATIONALE</strong></p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n The purpose of this study is to assess the efficacy and safety of a novel immunotherapy candidate, tobemstomig, in combination with nab-paclitaxel, for patients with previously untreated, locally advanced, unresectable or metastatic (Stage IV) programmed death-ligand 1 (PD-L1)-positive triple-negative breast cancer (TNBC).</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Breast cancer is the most frequently diagnosed cancer among women, and the leading cause of cancer-related deaths in women worldwide. TNBC accounts for 12%-20% of newly diagnosed breast cancer cases.</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n  </p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n This study will randomize in a 1:1 ratio to one of two treatment arms:</p>\n<ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <li style=\"line-height: 20px;\">\n Arm A: tobemstomig plus nab-paclitaxel – Participants will receive blinded tobemstomig, administered every 3 weeks (a “cycle”), plus nab‑paclitaxel, administered weekly on a repeating schedule of 3 weeks on followed by 1 week off, until disease progression or treatment discontinuation</li>\n <li style=\"line-height: 20px;\">\n Arm B: Pembrolizumab plus nab-paclitaxel – Participants will receive blinded pembrolizumab, administered every 3 weeks (a “cycle”), plus nab‑paclitaxel, administered weekly on a repeating schedule of 3 weeks on followed by 1 week off, until disease progression or treatment discontinuation.</li>\n</ul>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n The first approximately 12 participants will be included in a safety run-in period in which participants will be randomized equally to tobemstomig plus nab-paclitaxel or pembrolizumab plus nab-paclitaxel (targeting 6 participants on each combination). The remaining participants will continue to be randomized in a 1:1 ratio to receive TOBEMSTOMIG plus nab-paclitaxel or pembrolizumab plus nab-paclitaxel</div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n  </div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>Number of patients</strong></div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Approximately 160 patients (1:1 ratio in arm A and B)</div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n  </div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>End of Study:</strong></div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n  A participant is considered to have completed the study if he or she has completed all phases of the study including the last visit/last scheduled procedure shown in the schedule of activities (see Section 1.3 of protocol). The end of this study is defined as the date of the last visit of the last participant in the study or the date at which the last data point required for statistical analysis or safety follow-up is received from the last participant, whichever occurs later. In addition, the Sponsor may decide to terminate the study at any time  </div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n  </div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n  </div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n  </div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>Study Duration</strong></div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n The total duration of study participation for each individual is expected to range from 1 day to more than 30 months.</div>\n
      • study_title<div>\n A PHASE II, MULTICENTER, RANDOMIZED, DOUBLE-BLIND STUDY OF TOBEMSTOMIG/RO7247669 COMBINED WITH NAB-PACLITAXEL COMPARED WITH</div>\n<div>\n PEMBROLIZUMAB COMBINED WITH NABPACLITAXEL IN PARTICIPANTS WITH PREVIOUSLY UNTREATED, PD-L1-POSITIVE, LOCALLY-ADVANCED UNRESECTABLE OR METASTATIC TRIPLE-NEGATIVE BREAST CANCER</div>\n
      • laymans_summary<p>\n A Study of Tobemstomig/RO7247669 Combined With Nab-Paclitaxel Compared With Pembrolizumab Combined With Nab-Paclitaxel in Participants With Previously Untreated, PD-L1-Positive, Locally-Advanced Unresectable or Metastatic Triple-Negative Breast Cancer</p>\n
      • short_titleTNBC
      • protocol_noECCT/24/04/04
      • version_no4
      • date_of_protocol13-09-2023
      • study_drugTobemstomig
      • disease_conditionTRIPLE-NEGATIVE BREAST CANCER
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals1
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorYes
      • comparator_namePembolizumab & Nab-Paclitaxel
      • comparator_registeredYes
      • comparator_countriesGlobally
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressarpna.patel@roche.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantMilena Ruseva
      • declaration_date101-09-2024
      • declaration_principal_investigatorProf. Mansoor Saleh
      • declaration_date201-09-2024
      • placebo_presentNo
      • study_objectives<p>\n <span style=\"color: rgb(0, 0, 0); font-family: Arial, Helvetica, sans-serif; font-size: 11px;\">Breast cancer is the most frequently diagnosed cancer among women, and the leading cause of cancer-related deaths in women worldwide. TNBC accounts for 12% - 20% of newly diagnosed breast cancer cases. TNBC is characterized immunohistologically by the lack of expression of hormonal estrogen receptor (ER) and progesterone receptor (PgR), and lack of overexpression and/or amplification of the human epidermal growth factor receptor 2 (HER2)/neuraminidase (NEU) gene. Compared with other breast cancer subtypes, TNBC tumors are generally larger in size, more poorly differentiated, have more extensive lymph node involvement at diagnosis, and exhibit an invasive phenotype. Patients with TNBC have a higher risk of both local and distant recurrence, and metastases are more likely to occur in visceral organs and the brain, rather than bone, when compared with patients with other breast cancers. Patients with metastatic TNBC have relatively poorer outcomes. The purpose of this study is to assess the efficacy and safety of a novel immunotherapy candidate, tobemstomig, in combination with nab-paclitaxel, for patients with previously untreated, locally advanced, unresectable or metastatic (Stage IV) programmed death-ligand 1 (PD-L1)-positive triple-negative breast cancer (TNBC).</span></p>\n
      • principal_inclusion_criteria<ul style=\"box-sizing: inherit; color: rgb(27, 27, 27); font-family: Roboto, sans-serif; font-size: 16px;\">\n <li style=\"box-sizing: inherit;\">\n Metastatic or locally advanced unresectable, histologically documented triple-negative breast cancer (TNBC) (absence of HER2-over-expression, ER, and PgR expression by local assessment)</li>\n <li style=\"box-sizing: inherit;\">\n HER2-low-status</li>\n <li style=\"box-sizing: inherit;\">\n Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1</li>\n <li style=\"box-sizing: inherit;\">\n If metastatic disease (Stage IV), measurable disease outside of the bone</li>\n <li style=\"box-sizing: inherit;\">\n No prior systemic therapy for metastatic or locally advanced unresectable TNBC</li>\n <li style=\"box-sizing: inherit;\">\n Tumor PD-L1 expression as documented through central testing of a representative tumor tissue specimen</li>\n <li style=\"box-sizing: inherit;\">\n Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1</li>\n <li style=\"box-sizing: inherit;\">\n Adequate hematologic and end-organ function</li>\n <li style=\"box-sizing: inherit;\">\n Negative HIV test at screening, with the following exception: individuals with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count ≥ 200/uL, and have an undetectable viral load</li>\n <li style=\"box-sizing: inherit;\">\n Negative hepatitis B surface antigen (HBsAg) test at screening</li>\n <li style=\"box-sizing: inherit;\">\n Positive hepatitis B surface antibody (HBsAb) test at screening, or a negative HBsAb at screening accompanied by either of the following: negative hepatitis B core antibody (HBcAb); positive HBcAb test followed by quantitative hepatitis B virus (HBV) DNA < 500 IU/mL</li>\n <li style=\"box-sizing: inherit;\">\n Negative hepatitis C virus (HCV) antibody test at screening, or a positive HCV antibody test followed by a negative HCV RNA test at screening</li>\n <li style=\"box-sizing: inherit;\">\n Adequate cardiovascular function</li>\n</ul>\n
      • principal_exclusion_criteria<ul style=\"box-sizing: inherit; color: rgb(27, 27, 27); font-family: Roboto, sans-serif; font-size: 16px;\">\n <li style=\"box-sizing: inherit;\">\n Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 4 months after the final dose of tobemstomig or pembrolizumab, and 6 months after the final dose of nab-paclitaxel</li>\n <li style=\"box-sizing: inherit;\">\n Poor venous access</li>\n <li style=\"box-sizing: inherit;\">\n History of malignancy within 5 years prior to consent, except for the cancer under investigation in this study and malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate >90%), such as adequately treated carcinoma in situ of the cervix, nonmelanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer</li>\n <li style=\"box-sizing: inherit;\">\n Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases</li>\n <li style=\"box-sizing: inherit;\">\n History of leptomeningeal disease</li>\n <li style=\"box-sizing: inherit;\">\n Pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)</li>\n <li style=\"box-sizing: inherit;\">\n Hypercalcemia or hypercalcemia that is symptomatic</li>\n <li style=\"box-sizing: inherit;\">\n Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis (granulomatosis with polyangiitis), Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis</li>\n <li style=\"box-sizing: inherit;\">\n History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted</li>\n <li style=\"box-sizing: inherit;\">\n Active tuberculosis (TB)</li>\n <li style=\"box-sizing: inherit;\">\n Significant cardiovascular/cerebrovascular disease within 3 months prior to consent</li>\n <li style=\"box-sizing: inherit;\">\n History or presence of an abnormal ECG that is deemed clinically significant</li>\n <li style=\"box-sizing: inherit;\">\n History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias such as structural heart disease (e.g., severe left ventricular systolic dysfunction, left ventricular hypertrophy), coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing), clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia), or family history of sudden unexplained death or long QT syndrome</li>\n <li style=\"box-sizing: inherit;\">\n Major surgical procedure within 4 weeks prior to initiation of study treatment</li>\n <li style=\"box-sizing: inherit;\">\n Treatment with therapeutic oral or IV antimicrobials (anti-bacterial, anti-fungal, antiviral, anti-parasitic) within 1 week prior to initiation of study treatment</li>\n <li style=\"box-sizing: inherit;\">\n Prior allogeneic stem cell or solid organ transplantation</li>\n <li style=\"box-sizing: inherit;\">\n Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the participant at high risk from treatment complications</li>\n <li style=\"box-sizing: inherit;\">\n Treatment with a live, attenuated vaccine within 28 days prior to initiation of study treatment</li>\n <li style=\"box-sizing: inherit;\">\n Treatment with investigational therapy within 28 days prior to initiation of study treatment</li>\n <li style=\"box-sizing: inherit;\">\n Prior treatment with CD137 agonists or anti-CTLA therapeutic antibodies or an anti-LAG3 agent</li>\n <li style=\"box-sizing: inherit;\">\n Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and IL-2) within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment</li>\n <li style=\"box-sizing: inherit;\">\n Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including, but not limited to, prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF agents) within 2 weeks prior to initiation of study treatment</li>\n <li style=\"box-sizing: inherit;\">\n History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins</li>\n <li style=\"box-sizing: inherit;\">\n Known hypersensitivity to Chinese hamster ovary cell products or to any component of the tobemstomig or pembrolizumab formulation</li>\n <li style=\"box-sizing: inherit;\">\n Known allergy or hypersensitivity to any component of the to nab-paclitaxel formulation</li>\n</ul>\n
      • primary_end_points<div>\n progression-free survival, defined as the time from randomization to the first occurrence of disease progression, as determined by the investigator according to RECIST v1.1, or death from any cause (whichever occurs first).</div>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic1
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory1
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">This has been elaborated in the the respective site specific addendum attached in the checklist section.</span></p>\n
      • other_details_explanation<p>\n N/A</p>\n
      • other_details_regulatory_notapproved<p dir=\"ltr\" style=\"color: rgb(0, 0, 0); font-family: arial, sans-serif; font-size: small; line-height: 1.38; margin-left: 36pt; margin-top: 0pt; margin-bottom: 10pt;\">\n <span style=\"font-size: 11pt; font-family: Arial, sans-serif; background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; vertical-align: baseline;\">Clinical trial applications (CTAs) for Study CO44194 have been submitted to the health authorities of the following countries:</span></p>\n<ul style=\"color: rgb(0, 0, 0); font-family: arial, sans-serif; font-size: small; margin-top: 0px; margin-bottom: 0px;\">\n <li dir=\"ltr\" style=\"margin-left: 36pt; list-style-type: disc; font-size: 11pt; font-family: Arial, sans-serif; background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; vertical-align: baseline; white-space-collapse: preserve;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height: 1.38; margin-top: 10pt; margin-bottom: 0pt;\">\n <span style=\"font-size: 11pt; color: rgb(48, 48, 48); font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; vertical-align: baseline;\">Ghana on 28 December 2023</span></p>\n </li>\n <li dir=\"ltr\" style=\"margin-left: 36pt; list-style-type: disc; font-size: 11pt; font-family: Arial, sans-serif; color: rgb(48, 48, 48); background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; vertical-align: baseline; white-space-collapse: preserve;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height: 1.38; margin-top: 0pt; margin-bottom: 0pt;\">\n <span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; vertical-align: baseline;\">Nigeria on 5 January 2024</span></p>\n </li>\n <li dir=\"ltr\" style=\"margin-left: 36pt; list-style-type: disc; font-size: 11pt; font-family: Arial, sans-serif; background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; vertical-align: baseline; white-space-collapse: preserve;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height: 1.38; margin-top: 0pt; margin-bottom: 0pt;\">\n <span style=\"font-size: 11pt; color: rgb(48, 48, 48); font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; vertical-align: baseline;\">Ivory Coast on 23 January 2024</span></p>\n </li>\n <li dir=\"ltr\" style=\"margin-left: 36pt; list-style-type: disc; font-size: 11pt; font-family: Arial, sans-serif; color: rgb(48, 48, 48); background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; vertical-align: baseline; white-space-collapse: preserve;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height: 1.38; margin-top: 0pt; margin-bottom: 10pt;\">\n <span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; vertical-align: baseline;\">Uganda on 30 January 2024</span></p>\n </li>\n</ul>\n
      • other_details_regulatory_approved<ul style=\"color: rgb(0, 0, 0); font-family: arial, sans-serif; font-size: small; margin-top: 0px; margin-bottom: 0px;\">\n <li dir=\"ltr\" style=\"margin-left: 36pt; list-style-type: circle; font-size: 11pt; font-family: Arial, sans-serif; background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; vertical-align: baseline; white-space-collapse: preserve;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height: 1.38; margin-top: 10pt; margin-bottom: 0pt;\">\n <span style=\"font-size: 11pt; background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; vertical-align: baseline;\">In the United States (US), this trial was approved under IND 142906 (protocol v2), which was submitted to the FDA on 10 Nov 2022 and Study May Proceed Letter received on 9 Dec 2022. There are currently 6 active sites in the US. </span></p>\n </li>\n <li background-color:=\"\" dir=\"ltr\" font-variant-alternates:=\"\" font-variant-east-asian:=\"\" font-variant-numeric:=\"\" font-weight:=\"\" style=\"margin-left: 36pt; list-style-type: circle; font-size: 10.5pt; font-family: \" trebuchet=\"\" vertical-align:=\"\" white-space-collapse:=\"\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height: 1.38; margin-top: 0pt; margin-bottom: 0pt;\">\n <span style=\"font-size: 11pt; font-family: Arial, sans-serif; background-color: transparent; font-weight: 400; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; vertical-align: baseline;\">In the European Union (EU), Study CO44194 is considered a combined trial and the Sponsor has submitted documentation to comply with the Clinical Trial Regulation (CTR) and In Vitro Diagnostic Regulation (IVDR). A CTA submission was performed via the clinical trials information system (CTIS) on 24 April 2023. </span><span style=\"font-size: 11pt; font-family: Arial, sans-serif; color: rgb(34, 34, 34); font-weight: 400; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; vertical-align: baseline;\">Study CO44194 was approved with conditions (last country) under CTR on 22 August 2023. </span><span style=\"font-size: 11pt; font-family: Arial, sans-serif; background-color: transparent; font-weight: 400; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; vertical-align: baseline;\">A substantial modification (SM1) was submitted on 20 November 2023 and was approved on 16 February 2024. The clinical trial is currently authorized in the Czech Republic, Denmark, Germany, Italy, Spain, Netherlands, Poland and Hungary. However, recruitment can start only when the the documentation submitted nationally for the three devices (PD-L1 22C3 IHC Assay, PD-L1 SP142 IHC Assay and PD-L1 SP263 IHC Assay) used for the enrollment of patients onto clinical study CO44194 has received approval. Currently, the documentation related to the above-mentioned devices has been approved in the Czech Republic, Denmark, Netherlands, Poland, Spain, and Germany. Health authority approval is pending in Hungary and Italy. Currently, there are no active sites in the EU.</span></p>\n </li>\n <li dir=\"ltr\" style=\"margin-left: 36pt; list-style-type: circle; font-size: 11pt; font-family: Arial, sans-serif; background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; vertical-align: baseline; white-space-collapse: preserve;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height: 1.38; margin-top: 0pt; margin-bottom: 0pt;\">\n <span style=\"font-size: 11pt; background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; vertical-align: baseline;\">In addition, CO44194 clinical trial applications have been approved in:</span></p>\n <ul style=\"margin-top: 0px; margin-bottom: 0px;\">\n <li dir=\"ltr\" style=\"margin-left: 36pt; list-style-type: square; font-size: 11pt; background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; vertical-align: baseline;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height: 1.38; margin-top: 0pt; margin-bottom: 0pt;\">\n <span style=\"font-size: 11pt; background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; vertical-align: baseline;\">Turkey on 22 November 2023 (no active sites)  </span></p>\n </li>\n <li dir=\"ltr\" style=\"margin-left: 36pt; list-style-type: square; font-size: 11pt; background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; vertical-align: baseline;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height: 1.38; margin-top: 0pt; margin-bottom: 0pt;\">\n <span style=\"font-size: 11pt; background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; vertical-align: baseline;\">Mexico on 1 June 2023 (3 active sites)</span></p>\n </li>\n <li dir=\"ltr\" style=\"margin-left: 36pt; list-style-type: square; font-size: 11pt; background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; vertical-align: baseline;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height: 1.38; margin-top: 0pt; margin-bottom: 0pt;\">\n <span style=\"font-size: 11pt; background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; vertical-align: baseline;\">Argentina on 22 May 2023 (6 active sites)</span></p>\n </li>\n <li dir=\"ltr\" style=\"margin-left: 36pt; list-style-type: square; font-size: 11pt; background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; vertical-align: baseline;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height: 1.38; margin-top: 0pt; margin-bottom: 0pt;\">\n <span style=\"font-size: 11pt; background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; vertical-align: baseline;\">South Africa on 24 April 2023 (2 active sites)</span></p>\n </li>\n <li dir=\"ltr\" style=\"margin-left: 36pt; list-style-type: square; font-size: 11pt; background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; vertical-align: baseline;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height: 1.38; margin-top: 0pt; margin-bottom: 0pt;\">\n <span style=\"font-size: 11pt; background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; vertical-align: baseline;\">Peru on 29 December 2023 (no active sites)</span></p>\n </li>\n <li dir=\"ltr\" style=\"margin-left: 36pt; list-style-type: square; font-size: 11pt; background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; vertical-align: baseline;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height: 1.38; margin-top: 0pt; margin-bottom: 0pt;\">\n <span style=\"font-size: 11pt; background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; vertical-align: baseline;\">South Korea on 4 April 2023 (4 active sites)</span></p>\n </li>\n <li dir=\"ltr\" style=\"margin-left: 36pt; list-style-type: square; font-size: 11pt; background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; vertical-align: baseline;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height: 1.38; margin-top: 0pt; margin-bottom: 0pt;\">\n <span style=\"font-size: 11pt; background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; vertical-align: baseline;\">Israel on 15 March 2023 (3 active sites)</span></p>\n </li>\n <li dir=\"ltr\" style=\"margin-left: 36pt; list-style-type: square; font-size: 11pt; background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; vertical-align: baseline;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height: 1.38; margin-top: 0pt; margin-bottom: 0pt;\">\n <span style=\"font-size: 11pt; background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; vertical-align: baseline;\">Australia on 22 May 2023 (3 active sites)</span></p>\n </li>\n <li dir=\"ltr\" style=\"margin-left: 36pt; list-style-type: square; font-size: 11pt; background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; vertical-align: baseline;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height: 1.38; margin-top: 0pt; margin-bottom: 0pt;\">\n <span style=\"font-size: 11pt; background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; vertical-align: baseline;\">Brazil on 24 March 2023 (7 active sites)</span></p>\n </li>\n <li dir=\"ltr\" style=\"margin-left: 36pt; list-style-type: square; font-size: 11pt; background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; vertical-align: baseline;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height: 1.38; margin-top: 0pt; margin-bottom: 10pt;\">\n <span style=\"font-size: 11pt; background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; vertical-align: baseline;\">Taiwan on 14 April 2023 (4 active sites)</span></p>\n </li>\n </ul>\n </li>\n</ul>\n
      • other_details_regulatory_rejected<p>\n <span style=\"color: rgb(0, 0, 0); font-family: Arial, sans-serif; font-size: 14.6667px;\">No Health Authority has rejected a CTA for Study CO44194 to date.</span></p>\n
      • other_details_regulatory_halted<p>\n <span style=\"color: rgb(0, 0, 0); font-family: Arial, sans-serif; font-size: 14.6667px;\">Study CO44194 has not been halted at any stage by other Regulatory Authorities.</span></p>\n
      • estimated_duration49-55 months
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorPembrolizumab
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherYes
      • design_controlled_medicinal_specifyNab-Paclitaxel
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states24
      • number_of_sites3
      • multi_country_listARGENTINA, \nAUSTRALIA\nBRAZIL\nCOTE D\'IVOIRE\nDENMARK\nGERMANY\nGHANA\nHUNGARY\nISRAEL\nITALY\nKENYA\nKOREA, REPUBLIC OF\nMEXICO\nNETHERLANDS\nNIGERIA\nPERU\nPOLAND\nSOUTH AFRICA\nSPAIN\nSWITZERLAND\nTAIWAN\nUGANDA\nUNITED STATES
      • data_monitoring_committeeYes
      • total_enrolment_per_site10 per site
      • total_participants_worldwide160
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyYes
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameMansoor
      • investigator1_middle_name
      • investigator1_family_nameSaleh
      • investigator1_qualificationProfessor of Medicine & Pathology
      • investigator1_professional_addressHematology-Oncology, Aga Khan University Hospital, Nairobiya
      • investigator1_telephone +254 709 93 1500
      • investigator1_emailmansoor.saleh@aku.edu
      • organisations_transferred_Yes
      • number_participants30
      • notification
      • approval_date19-09-2024
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted04-06-2024
      • unsubmitted1
      • initial_date_submitted04-06-2024
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonApplication reviewed with satisfactory responses on evaluation comments
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2024-09-19 13:18:06
      • created2024-02-22 15:50:12
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id1040
        • application_id1379
        • given_nameMansoor
        • middle_name
        • family_nameSaleh
        • qualificationProfessor of Medicine & Pathology
        • professional_addressHematology-Oncology, Aga Khan University Hospital, Nairobi
        • telephone +254 709 93 1500
        • emailmansoor.saleh@aku.edu
        • created2024-02-22 15:51:08
        • modified2024-09-01 21:44:59
    • SiteDetail(array)
      • 0(array)
        • id1672
        • application_id1379
        • county_id47
        • site_nameUniversity of Nairobi - Institute of Tropical and Infectious Diseases
        • physical_addressFaculty of Health Sciences
        • contact_detailsBOX 19676-00202
        • contact_personDr. Pauline Njoki Njiraini
        • site_capacity(null)
        • misc(null)
        • created2024-02-22 15:51:08
        • modified2024-09-01 21:44:59
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 1(array)
        • id1689
        • application_id1379
        • county_id29
        • site_nameInternational Cancer Institute
        • physical_addressNandi Road 8/10, Eldoret, Kenya, 8088-30100
        • contact_details+254 700 52 2149
        • contact_personProf. Fredrick Chite Asirwa
        • site_capacity(null)
        • misc(null)
        • created2024-03-27 15:11:57
        • modified2024-09-01 21:44:59
        • County(array)
          • id29
          • county_nameNandi
          • created2012-06-15 10:25:33
          • modified2012-06-15 10:25:33
      • 2(array)
        • id1744
        • application_id1379
        • county_id47
        • site_nameThe Aga Khan University Hospital - Kenya
        • physical_address3rd Parklands Avenue Box 30270 Off Limuru Road 00100 Nairobi, Kenia
        • contact_details+254 709 93 1500
        • contact_personProf. Mansoor Saleh
        • site_capacity(null)
        • misc(null)
        • created2024-06-26 18:07:30
        • modified2024-09-01 21:44:59
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
    • Sponsor(array)
      • 0(array)
        • id725
        • application_id1379
        • sponsorHoffmann La Roche
        • sponsor_typeIndustry
        • contact_personMilena Ruseva
        • addressRoche Kenya Ltd, The atrium, Chaka Road
        • telephone_number00359887333827
        • fax_number
        • cell_number00359887333827
        • email_addressMilena.Ruseva@roche.com
        • created2024-02-22 15:51:08
        • modified2024-09-01 21:44:59
  • 3(array)
    • Application(array)
      • id1374
      • user_id693
      • trial_status_id1
      • abstract_of_study<p>\n Sudan ebolavirus (SUDV) is one of the 6 genera in the family <em>Filoviridae</em>, which, along with Marburgvirus and Cuevavirus, are known to induce viral hemorrhagic fever. SUDV is a large, negative-strand RNA virus composed of 7 genes encoding viral proteins, including a single glycoprotein (GP). In humans, SUDV is responsible for causing Sudan Ebolavirus Disease (SUVD). It spreads through human-to-human transmission, with infection resulting from direct contact with blood, secretions, organs, or other bodily fluids of infected people and indirect contact with contaminated environments. SUVD has an incubation period of 2 to 21 days followed by a rapid and abrupt onset of nonspecific symptoms such as fever, extreme fatigue, gastrointestinal complaints, abdominal pain, anorexia, headache, myalgias, and/or arthralgias, and diarrhea can persist for a week. Many patients develop severe hemorrhagic manifestations, including hemorrhagic rash, epistaxis, mucosal bleeding, hematuria, hemoptysis, hematemesis, melena, conjunctival hemorrhage, tachypnea, confusion, somnolence, and hearing loss between 5 and 7 days after infection. Laboratory findings include low white blood cell and platelet counts and elevated liver enzymes. In the last decades, SUDV has been associated with large outbreaks of SUVD in Africa; the average case fatality rate is around 50%, varying from 41% to 71% depending on virus strain and case management (<a href=\"https://ppdcentral-my.sharepoint.com/personal/phoebe_otieno_ppd_com/Documents/1.%20MY%20STUDIES/9.%20Sabin%20003/Protocol/Printed/Sabin-003%20Protocol%20v1.1%2017Oct2023%20redline.docx#WHO2021\">WHO 2021</a>).</p>\n<p>\n The SUDV is the etiologic agent of SUVD and has been associated with 8 major outbreaks; the 2 largest occurring in Africa (Sudan in 1976 and Uganda in 2000) that resulted in case fatality rates over 53%. The first recorded case of SUVD in Uganda occurred in August 2000 and resulted in 224 fatalities. (<a href=\"https://ppdcentral-my.sharepoint.com/personal/phoebe_otieno_ppd_com/Documents/1.%20MY%20STUDIES/9.%20Sabin%20003/Protocol/Printed/Sabin-003%20Protocol%20v1.1%2017Oct2023%20redline.docx#WHO2022\">WHO 2022</a>) Recently 55 fatal cases of SUVD were reported from several regions in Uganda as of January 2023 (<a href=\"https://ppdcentral-my.sharepoint.com/personal/phoebe_otieno_ppd_com/Documents/1.%20MY%20STUDIES/9.%20Sabin%20003/Protocol/Printed/Sabin-003%20Protocol%20v1.1%2017Oct2023%20redline.docx#WHO2023\">WHO 2023</a>). There is a continued potential threat of spread to other countries given the frequency of international travel (<a href=\"https://ppdcentral-my.sharepoint.com/personal/phoebe_otieno_ppd_com/Documents/1.%20MY%20STUDIES/9.%20Sabin%20003/Protocol/Printed/Sabin-003%20Protocol%20v1.1%2017Oct2023%20redline.docx#SabinIB\">IB 2023</a>).</p>\n<p>\n The primary goal of the cAd3-EBO S vaccine development program is to create a safe and effacacious vaccine that can induce rapid immunity followed by durable protection against SUVD. Sabin cAd3-EBO S vaccine is supplied as a single-dose vial that contains a recombinant chimpanzee adenovirus Type 3 (cAd3) vector that expresses wild-type (WT) GP from the Gulu strain of the SUDV.</p>\n<p>\n The cAd3 vector was selected as it has little to no pre-existing immunity in human populations, its superior immunogenicity in humans relative to DNA vaccines for other viral diseases, and its performance in Non-Human Primate (NHP) Ebolavirus challenge studies. A Phase 1 study (<a href=\"https://ppdcentral-my.sharepoint.com/personal/phoebe_otieno_ppd_com/Documents/1.%20MY%20STUDIES/9.%20Sabin%20003/Protocol/Printed/Sabin-003%20Protocol%20v1.1%2017Oct2023%20redline.docx#NIAID2022\">RV508</a>) evaluated the safety, tolerability, and immunogenicity of the SUDV chimpanzee adenovirus vector vaccine, VRC-EBOADC086-00-PU (cAd3-EBO S), in healthy adults at the Makerere University Walter Reed Project in Kampala, Uganda. Tachypnoea was the most commonly reported unsolicited AE, occurring in 12 of 40 subjects (30%). Overall, the cAd3-EBO S vaccine was well-tolerated. There were no deaths or SAEs related to the product (<a href=\"https://ppdcentral-my.sharepoint.com/personal/phoebe_otieno_ppd_com/Documents/1.%20MY%20STUDIES/9.%20Sabin%20003/Protocol/Printed/Sabin-003%20Protocol%20v1.1%2017Oct2023%20redline.docx#NIAID2022\">NCT04041570</a>). Further, a Phase 1 study (<a href=\"https://ppdcentral-my.sharepoint.com/personal/phoebe_otieno_ppd_com/Documents/1.%20MY%20STUDIES/9.%20Sabin%20003/Protocol/Printed/Sabin-003%20Protocol%20v1.1%2017Oct2023%20redline.docx#Sabin2022\">Sabin-001</a>) evaluated the safety, tolerability, and immunogenicity of cAd3-EBO S in healthy adults at the Oklahoma Blood Institute in Oklahoma City, Oklahoma. A total of 14 unsolicited adverse events were reported by 9 of 16 (56.3%) subjects, of which 4 (28.6%) events were assessed related to study product administration. Related events included one subject who developed a feeling of body temperature change (mild) and fatigue. One subject reported moderate malaise and another subject developed mild lymphadenopathy. All related events resolved within 3 days and without sequalae. There were no deaths or Serious Adverse Events (SAEs) related to the product (<a href=\"https://ppdcentral-my.sharepoint.com/personal/phoebe_otieno_ppd_com/Documents/1.%20MY%20STUDIES/9.%20Sabin%20003/Protocol/Printed/Sabin-003%20Protocol%20v1.1%2017Oct2023%20redline.docx#Sabin2022\">NCT04723602</a>).</p>\n<p>\n Similarly, a Phase 1, dose-escalation, open-label study of cAd3-EBO S conducted at the National Institutes of Health (NIH) Clinical Center in Bethesda, Maryland supported the safety and immunogenicity of a single vaccination. The rates and severity of local and systemic side effects, including fever at higher dose levels, were similar to those observed in previous studies of other adenovirus vectors (<a href=\"https://ppdcentral-my.sharepoint.com/personal/phoebe_otieno_ppd_com/Documents/1.%20MY%20STUDIES/9.%20Sabin%20003/Protocol/Printed/Sabin-003%20Protocol%20v1.1%2017Oct2023%20redline.docx#Ledgerwood2017\">Ledgerwood 2017</a>). A Phase 2 randomized, observer-blind, placebo-controlled study on the safety, reactogenicity, and immunogenicity of a chimpanzee adenovirus vectored Ebola vaccine in adults conducted at multiple investigational sites in Bamenda and Yaounde, Cameroon, Bamako, Mali, Abuja, Nigeria, and Dakar, Senegal showed it was immunogenic and well tolerated in adults (<a href=\"https://ppdcentral-my.sharepoint.com/personal/phoebe_otieno_ppd_com/Documents/1.%20MY%20STUDIES/9.%20Sabin%20003/Protocol/Printed/Sabin-003%20Protocol%20v1.1%2017Oct2023%20redline.docx#Tapia2020\">Tapia 2020</a>).</p>\n<p>\n Moreover, chimpanzee adenoviral vector vaccines targeting other diseases have been generally safe in healthy adults at dosages up to 1 × 10¹¹ Viral Particles (VP) per injection in completed and ongoing clinical trials. Systemic reactogenicity typically occurs on the day of or day after vaccination and may include headache, malaise, myalgia, chills, and fever. When present, fever onset occurs within 1 day of vaccination and typically resolves within 24 hours of onset. A pattern of fever occurring later than 1 day after vaccination or lasting longer than 1 day may require evaluation for additional etiology (<a href=\"https://ppdcentral-my.sharepoint.com/personal/phoebe_otieno_ppd_com/Documents/1.%20MY%20STUDIES/9.%20Sabin%20003/Protocol/Printed/Sabin-003%20Protocol%20v1.1%2017Oct2023%20redline.docx#Ledgerwood2017\">Ledgerwood 2017</a>). Risks of the vaccine to pregnant and nursing women and to the unborn fetus are unknown. As such, women of reproductive potential will be required to agree to use birth control beginning at least 21 days prior to enrollment and continue through 24 weeks after study vaccination. There may be other unknown side effects. Blood drawing with needles, like injections, may cause pain, bruising, feeling lightheaded, fainting, possible nerve injury and, rarely, infection at the site where the blood is taken.</p>\n<p>\n Although study participants may benefit from clinical evaluations, laboratory testing and physical examinations (during assessment of eligibility), study participants will receive no direct benefit from participation.</p>\n<p>\n Detailed information about the known and expected benefits and risks and reasonably expected Adverse Events (AEs) of the Investigational Product (IP) is provided in the investigator’s brochure (<a href=\"https://ppdcentral-my.sharepoint.com/personal/phoebe_otieno_ppd_com/Documents/1.%20MY%20STUDIES/9.%20Sabin%20003/Protocol/Printed/Sabin-003%20Protocol%20v1.1%2017Oct2023%20redline.docx#SabinIB\">IB 2023</a>).</p>\n
      • study_title<p>\n A Phase 2, Randomized, Double-blind, Placebo-Controlled Trial to Evaluate Safety, Tolerability, and Immune Responses of an Investigational Monovalent Chimpanzee Adenoviral-Vectored Sudan Ebolavirus Vaccine in Healthy Adults</p>\n
      • laymans_summary<p>\n In humans, Sudan Ebolavirus (SUDV) is responsible for causing Sudan Ebolavirus Disease (SUVD), formerly known as Ebola hemorrhagic fever. It spreads through human-to-human transmission, with infection resulting from direct contact with blood, secretions, organs, or other bodily fluids of infected people, and indirect contact with contaminated environments. The average case fatality rate of SUVD is around 50%.</p>\n<p>\n SUDV has an incubation period of 2 to 21 days followed by a rapid and abrupt onset of nonspecific symptoms such as fever, extreme fatigue, gastrointestinal complaints, abdominal pain, anorexia, headache, myalgias, and/or arthralgias, and diarrhea that can persist for a week. Many patients develop severe hemorrhagic manifestations, including hemorrhagic rash, epistaxis, mucosal bleeding, hematuria, hemoptysis, hematemesis, melena, conjunctival hemorrhage, tachypnea, confusion, somnolence, and hearing loss between 5 and 7 days after infection. The SUDV has been associated with 8 major outbreaks, mainly in Africa. There is a continued potential threat of spread to other countries given the frequency of international travel.</p>\n<p>\n As there are currently no approved vaccines or therapeutics to treat individuals infected with SUDV, a vaccine with rapid and durable protective immunity would be desirable for populations in areas of the world where outbreaks occur sporadically.</p>\n<p>\n The primary goal of the cAd3-EBO S vaccine development program is to create a safe and effacacious vaccine that can induce rapid immunity followed by durable protection against SUVD. Sabin cAd3-EBO S vaccine is supplied as a single-dose vial that contains a recombinant chimpanzee adenovirus Type 3 (cAd3) vector that expresses wild-type (WT) glycoprotein (GP) from the Gulu strain of the SUDV.</p>\n<p>\n Previous studies have evaluated the safety and immunogenicity of the cAd3-EBO S vaccine in a small group of healthy adults up to 50 years of age in the United States. This Phase 2 study will evaluate the safety, tolerability, and immunogenicity of the cAd3-EBO S vaccine in healthy adults up to 70 years of age in an African population.</p>\n
      • short_titleSabin 003
      • protocol_noECCT/24/02/02
      • version_noVersion 1.1
      • date_of_protocol17-10-2023
      • study_drugcAd3-EBO S vaccine
      • disease_conditionEbola virus Disease
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines1
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressPPDSubmissionsMembers.SM@ppd.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantPhoebe Mercy Otieno
      • declaration_date106-02-2024
      • declaration_principal_investigatorProf. Vitalis Nduba
      • declaration_date206-02-2024
      • placebo_presentYes
      • study_objectives<p>\n Primary Objective</p>\n<p>\n To evaluate the safety and tolerability of cAd3-EBO S vaccine</p>\n<p>\n Key secondary objective</p>\n<p>\n To evaluate the antibody response (IgG) to cAd3‑EBO S vaccine at Day 29 post-vaccination.</p>\n<p>\n Other secondary objective</p>\n<p>\n To determine the antibody (IgG) response to cAd3-EBO S vaccine across additional timepoints post-vaccination.</p>\n<p>\n Exploraroty objective</p>\n<p style=\"margin-left:16.8pt;\">\n ·       To describe the antibody response (IgM) to cAd3-EBO S vaccine.</p>\n<p style=\"margin-left:16.8pt;\">\n ·       To describe the neutralizing antibody response to cAd3-EBO S vaccine.</p>\n<p style=\"margin-left:16.8pt;\">\n ·       If deemed necessary, to further characterize the immune response of the cAd3-EBO S investigational vaccine</p>\n
      • principal_inclusion_criteria<p>\n Each participant must meet all of the following criteria to be enrolled in this study:</p>\n<ol>\n <li>\n Able and willing to complete and provide written informed consent prior to any study procedure, completing an Assessment of Understanding (AoU) prior to enrollment by answering 9 out of 10 questions correctly at least once in 3 attempts, and including optional consent for retention of blood samples for potential future testing and assay development.</li>\n</ol>\n<p style=\"margin-left:.45in;\">\n Note: Participants can be enrolled even if they do not provide optional consent for retention of blood samples for potential future testing and assay development.</p>\n<ol>\n <li value=\"2\">\n Able to read and write the language used in diary card.</li>\n <li value=\"3\">\n Male or non-pregnant female 18 to 70 years of age (inclusive) at time of informed consent.</li>\n <li value=\"4\">\n Is capable of understanding and agrees to comply with planned study procedures and to be available for all clinic follow-up for all planned study visits.</li>\n <li value=\"5\">\n Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process.</li>\n <li value=\"6\">\n Has a means to be contacted and to contact the investigator during the study.</li>\n <li value=\"7\">\n Agree not to receive any vaccine within 28 days from study vaccination (prior and after), with the exception of an emergency use authorization or authorized non‑adenoviral vectored COVID‑19 vaccine, which may be given within 14 days of study vaccination.</li>\n <li value=\"8\">\n Agree not to donate bone marrow, blood, or blood products until 3 months after the study vaccination.</li>\n <li value=\"9\">\n In good general health without clinically significant medical conditions, based on medical history, physical examination, vital signs, and clinical laboratory results as deemed acceptable by the principal investigator.</li>\n <li value=\"10\">\n Clinical laboratory results within 28 days prior to vaccination within the site’s laboratory reference ranges (or deemed not clinically significant by the principal investigator) for the following parameters: hematology (CBC including hemoglobin, WBC, RBC, total lymphocyte count); coagulation tests (prothrombin time, d‑dimer, INR, fibrinogen); chemistry (C-reactive protein, ALT, AST, and serum creatinine). A laboratory result that is outside the reference range and is deemed not clinically significant by the principal investigator will not exclude the participant.</li>\n <li value=\"11\">\n Has a BMI >17 and ≤37 at screening.</li>\n</ol>\n<p>\n <strong><u>Female participant-specific criteria:</u></strong></p>\n<ol>\n <li value=\"12\">\n Negative pregnancy serum test at screening, and negative urine pregnancy test before vaccination, if of reproductive potential.</li>\n <li value=\"13\">\n Agrees to use an effective means of birth control from at least 21 days prior to enrollment through 24 weeks after study vaccination if assessed to be woman of childbearing potential UNLESS they fulfill one of the following criteria:</li>\n</ol>\n<ul>\n <li>\n At least 1 year postmenopausal.</li>\n <li>\n Surgically sterile.</li>\n</ul>\n<p>\n <strong><u>Male participants must agree:</u></strong></p>\n<ol>\n <li value=\"14\">\n Not to father a child or donate sperm through study end.</li>\n <li value=\"15\">\n To use a barrier (condom) means of birth control from vaccination through study end, if assessed to be of reproductive potential.</li>\n</ol>\n<h3>\n  </h3>\n
      • principal_exclusion_criteria<h3>\n 1.1.1Exclusion Criteria</h3>\n<p>\n Participants meeting any of the following criteria will be excluded from the study:</p>\n<ol>\n <li>\n Pregnant or lactating female or plans to become pregnant or breastfeed starting from study vaccination through to study end.</li>\n <li>\n Has any medical disease or condition that, in the opinion of the investigator, precludes study participation. This includes any acute, subacute, intermittent, or chronic medical disease or condition that:</li>\n</ol>\n<ul>\n <li>\n would place the participant at an unacceptable risk of injury,</li>\n <li>\n render the participant unable to comply with the requirements of the protocol,</li>\n <li>\n or may interfere with the evaluation of responses or the participant's successful completion of the trial (chronic conditions that are well-controlled and medically stable, <em>i.e.</em>, no change in treatment for medical reasons occurred in the last 6 months and are allowed at the discretion of the principal investigator, <em>e.g.</em>, hypertension, asthma, thyroid disease).</li>\n</ul>\n<p style=\"margin-left: 0.2in;\">\n The medical disease or condition also includes any confirmed or suspected immunosuppressive or immunodeficient conditions resulting from disease (<em>e.g.</em>, malignancy, HIV infection) or immunosuppressive/cytotoxic therapies (<em>e.g.</em>, medications used during cancer chemotherapy, organ transplantation or to treat autoimmune disorders).</p>\n<ol>\n <li value=\"3\">\n Serology screen positive for infectious diseases (hepatitis B, hepatitis C, HIV 1 and 2, syphilis).</li>\n <li value=\"4\">\n Known history of prior exposure to SUDV or prior diagnosis of SUVD, determined from the participant’s reported medical history.</li>\n <li value=\"5\">\n Current diagnosis of COVID-19 by Reverse Transcription Polymerase Chain Reaction (RT-PCR) or antigenic testing or current signs and symptoms of COVID-19. Participants may be enrolled 14 days post resolution of all signs and symptoms of COVID-19 or of testing positive for COVID-19 in asymptomatic participants.</li>\n <li value=\"6\">\n History of or active status of any of the following clinically significant conditions:</li>\n</ol>\n<ul>\n <li>\n Serious adverse reactions to vaccines such as anaphylaxis, urticaria (hives), respiratory difficulty, angioedema, or abdominal pain.</li>\n <li>\n Allergic reaction to excipients in the study vaccine including gentamycin, neomycin or streptomycin or any other aminoglycoside.</li>\n <li>\n Diabetes mellitus type 1 or type 2.</li>\n <li>\n Active tuberculosis.</li>\n <li>\n Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema.</li>\n <li>\n Idiopathic urticaria within the last year.</li>\n <li>\n Bleeding disorder diagnosed by a doctor (<em>e.g.</em>, factor deficiency, coagulopathy, or platelet disorder requiring special precautions), use of anticoagulant medications such as warfarin, apixaban, or dabigatran, or significant bruising or bleeding difficulties with IM injections or blood draws.</li>\n <li>\n Major thrombotic event or heparin-induced thrombocytopenia or Vaccine-Induced Thrombotic Thrombocytopenia (VITT).</li>\n <li>\n Malignancy of any organ system, treated or untreated, within the past 5 years from screening (if diagnosed malignancy is 5 or more years prior to enrollment and cured with no ongoing treatment it will NOT be considered an exclusion).</li>\n <li>\n Seizure in the past 3 years or treatment for seizure disorder in the past 3 years.</li>\n <li>\n Asplenia or functional asplenia.</li>\n <li>\n Autoimmune disease/autoinflammatory condition.</li>\n <li>\n Any medical, psychiatric, social condition, occupational reason, or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a participant’s ability to give informed consent.</li>\n</ul>\n<ol>\n <li value=\"7\">\n Has a clinically significant acute illness (this does not include minor illnesses) or temperature ≥38.0°Celsius (≥100.4° Fahrenheit) within 24 hours of the planned dose of study vaccine. Re‑evaluation of eligibility may be performed at resolution of all signs and symptoms, and randomization at a later date is permitted at the discretion of the investigator and after consultation with the sponsor (as appropriate).</li>\n <li value=\"8\">\n Receipt of any of the following substances:</li>\n</ol>\n<ul>\n <li>\n COVID‑19 vaccine that has not received emergency use authorization or approval per local regulatory agency.</li>\n <li>\n Prior receipt of Ebola or Marburg vaccine.</li>\n <li>\n Prior receipt of any adenoviral-vectored vaccine, adenovirus-based or adeno-associated virus (AAV)-based gene therapies or treatments, including adenoviral COVID-19 vaccines or boosters.</li>\n <li>\n Participant received an investigational drug (including investigational drugs for prophylaxis of COVID-19) within 28 days of dosing or within washout period (5 half-lives) of such drug or has used an invasive investigational medical device within 28 days of dosing.</li>\n <li>\n Received investigational Ig or monoclonal antibodies within 3 months.</li>\n <li>\n Received convalescent serum for COVID-19 treatment within 3 months.</li>\n <li>\n Received an investigational vaccine within 3 months before the planned administration of the first dose of study vaccine.</li>\n <li>\n Is currently enrolled or plans to participate in another investigational or interventional study during this study (observational/registry studies are allowed).</li>\n</ul>\n<ol>\n <li value=\"9\">\n Use of immunomodulators or systemic glucocorticoids in daily doses of glucocorticoid equivalence >20 mg of prednisolone in the last 90 days, and for periods exceeding 10 days. Non-Steroidal Anti-Inflammatory Drugs (NSAIDS) are permitted.</li>\n <li value=\"10\">\n Receipt of blood products within 3 months prior to enrollment.</li>\n <li value=\"11\">\n Current anti-tuberculosis prophylaxis or therapy.</li>\n <li value=\"12\">\n Abnormality or permanent body art (such as tattoo) in deltoid region that would interfere with ability to observe or assess injection site reactions.</li>\n</ol>\n
      • primary_end_points<p>\n <em>Primary Endpoint: </em>Count and percentage of vaccinated participants who develop:</p>\n<p style=\"margin-left:17.0pt;\">\n ·       SAEs,</p>\n<p style=\"margin-left:17.0pt;\">\n ·       solicited AEs,</p>\n<p style=\"margin-left:17.0pt;\">\n ·       unsolicited AEs,</p>\n<p style=\"margin-left:17.0pt;\">\n ·       AESI,</p>\n<p style=\"margin-left:17.0pt;\">\n ·       MAAE,</p>\n<p style=\"margin-left:17.0pt;\">\n ·       AE at each intensity level.</p>\n<p>\n Estimand 1a (Primary): Count and percentage of vaccinated participants who would develop SAEs, solicited AEs, unsolicited AEs, AESI, MAAE, and AE at each intensity level will be evaluated with each treatment group. A treatment policy strategy is used for assessing safety irrespective of a current (or prior) infection at time of the vaccination. Infections and death (if they meet the AE and time window criteria) are included in the endpoint (composite strategy).</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy0
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others1
      • scope_others_specifyTolerability, and Immune Responses
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory1
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Site activities will be located in Siaya County at the Siaya County Referral Hospital grounds at the Clinical Research Annex. Siaya site is a modern research facility, well equipped with capacity to conduct this vaccine trial. All the study activities will be conducted at the Clinical Research Site. After community mobilization, recruitment, screening and enrollment, IP storage and dispensation (vaccinations) will occur at the Siaya Research Annex. The site has conducted more than 20 clinical trials since establishment.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  The site lab is well equipped with the necessary equipment and capacity to collect, process, store and manage the collected study samples. The equipments are well maintained with regular calibration. The site laboratory staff are qualified by education, training and experience. In addition, they are GCLP and Laboratory IATA trained and Certified. The Site pharmacy is equipped with fridges and temperature monitoring devices for IP management.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n The site is ICH/GCP compliant with all staff undertaking the GCP and ethics training prior to conducting the delegated duties. In addition, the community team is GPP compliant with good recruitment and retention plan that is goal oriented.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Site Personnel responsible for day to day running of the project include a Principal Investigator, 2 Medical Officers, 2 Pharmacists, 2 Pharmaceutical Technologists, 6 Nurses, 6 QA/QC officers, 4 Clinical Officers,4 Laboratory Technologists, 2 Administrative Officers, 4 Data personnel and 7 Community Interviewers. This clinical research team is well trained and experienced in data collection including eligibility assessment and participant care during follow up.</p>\n
      • other_details_explanation<p>\n <em font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">A prior study </em><em font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">for this IP have been conducted in the United States (?in a predominantly Caucasian population):</em></p>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n <em>Sabin-001, a Phase 1b,  clinical trial evaluating the safety, tolerability and immune responses of two cAd3-vectored IP (Ebola Sudan and Marburg) where a total of 16 participants received a 1 x 10<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; top: -0.5em;\">11</span> PU dose of cAd3-Marburg vaccine by IM route. The IP overall was generally well tolerated, with all reported reactogenicity being mild to moderate in severity.</em></li>\n</ol>\n<p style=\"line-height: 20px;\">\n <em font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">Sabin-003 is a phase 2 study, building on the study results above, intended to evaluate the safety, tolerability, and immunogenicity of the same product, for generalizable study data in an African population, that is likely to have markedly different prior exposure to the cAd3 vector (and other pathogens that may impact on immunogencity); as well as potential for further  differences in immunogenicity due to different genetics.</em></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <em>As defined in the Site-specific addendums, both countries are at risk of Ebola outbreaks, and assessing the safety, tolerability and immune responses of this study in this population is pertinent to this population</em>.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n
      • other_details_regulatory_notapproved<p>\n Application not yet done to Uganda NDA. </p>\n
      • other_details_regulatory_approved<p>\n None</p>\n
      • other_details_regulatory_rejected<p>\n Not rejected in any country </p>\n
      • other_details_regulatory_halted<p>\n None </p>\n
      • estimated_duration18Months
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorPlacebo _Normal Saline
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKEMRI / CRDR, KEMRI Clinical Research Annex, Siaya County Referral Hospital Ground. P.O BOX 144-40600 ,Siaya, Kenya
      • single_site_physical_addressP.O BOX 144-40600 ,Siaya, Kenya
      • single_site_contact_personDr. Videlis Nduba
      • single_site_telephone+254724522474
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states2
      • number_of_sites
      • multi_country_list2
      • data_monitoring_committeeYes
      • total_enrolment_per_site80
      • total_participants_worldwide160
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyYes
      • gender_female1
      • gender_male1
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsNo
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameProf. Videlis Nduba
      • investigator1_middle_name
      • investigator1_family_nameNzioka
      • investigator1_qualificationGeneral practice
      • investigator1_professional_addressKEMRI / CRDR, KEMRI Clinical Research Annex, Siaya County Referral Hospital Ground. P.O BOX 144-40600 ,Siaya, Kenya
      • investigator1_telephone+254724522474
      • investigator1_emailvnduba@kemri.org
      • organisations_transferred_Yes
      • number_participants80
      • notification<p>\n None</p>\n
      • approval_date23-04-2024
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted06-02-2024
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have been addressed.
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2024-10-02 17:07:03
      • created2024-02-03 05:32:41
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id1037
        • application_id1374
        • given_nameProf. Videlis Nduba
        • middle_name
        • family_nameNzioka
        • qualificationGeneral practice
        • professional_addressKEMRI / CRDR, KEMRI Clinical Research Annex, Siaya County Referral Hospital Ground. P.O BOX 144-40600 ,Siaya, Kenya
        • telephone+254724522474
        • emailvnduba@kemri.org
        • created2024-02-03 05:53:15
        • modified2024-02-06 12:58:21
    • SiteDetail(array)
      • 0(array)
        • id1669
        • application_id1374
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2024-02-03 05:53:15
        • modified2024-02-06 12:58:21
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id722
        • application_id1374
        • sponsorSabin Vaccine Institute 2175 K Street, NW, Suite 400 Washington DC 20037
        • sponsor_typeResearch Institution
        • contact_personAntonio Gonzalez-Lopez, MD, PhD, MPH Vice President, Clinical Development
        • address2175 K Street, NW, Suite 400 Washington DC 20037
        • telephone_number+1-240-274-4546
        • fax_number
        • cell_number+1 240-274-4546
        • email_addressAntonio.GonzalezLopez@Sabin.org
        • created2024-02-03 05:53:15
        • modified2024-02-06 12:58:21
  • 4(array)
    • Application(array)
      • id1352
      • user_id263
      • trial_status_id(null)
      • abstract_of_study<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>Protocol Title:</strong></p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n A Phase 2a, Multicenter, Open-label, Dose-finding, Dose escalation Study of Meplazumab in Adult Patients diagnosed with Uncomplicated <em>Plasmodium falciparum</em> Malaria.</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>Rationale</strong><strong>:</strong></p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Meplazumab, an erythrocytic stage-macromolecular antibody drug, has the potential to control clinical occurrence of falciparum malaria. Meplazumab is a humanized anti-CD147 immunoglobulin G subclass 2 (IgG2) monoclonal antibody with strong affinity to CD147. CD147 is expressed on erythrocyte lineage cells throughout erythroid development, including mature erythrocytes and is the target for Plasmodium merozoites to allow reorientation and subsequent invasion of the erythrocytes. Nonclinical studies have demonstrated that meplazumab binding to CD147 interferes with the receptor‑ligand interaction between CD147 and rhoptry-associated protein 2 (RAP2) of the <em>P. falciparum</em> merozoite and inhibits the formation of parasitophorous vacuoles of <em>P. falciparum</em> thus preventing the invasion of <em>P. falciparum</em> into human erythrocytes. Furthermore, the therapeutic and prophylactic effects of meplazumab were demonstrated in vivo using a human erythrocyte chimeric NOG mouse model, which is considered as an optimal choice for in vivo inhibition efficacy study for human-hosted <em>P. falciparum</em>.</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Meplazumab has previously been studied in healthy participants in two Phase 1 studies and has also been evaluated for activity in 2 completed clinical trials in patients diagnosed with coronavirus disease 2019 (COVID‑19). In the safety, tolerability, and pharmacokinetics study in healthy participants, MPZ‑I-01, results demonstrated a high and prolonged receptor occupancy (RO%) of meplazumab at CD147.</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n This Phase 2a study is designed as a dose escalation trial to assess safety of meplazumab in the target population and to evaluate whether meplazumab is efficacious in treating malaria. The data obtained in this study will be used to determine a recommended meplazumab dose for future Phase 2b and 3 efficacy trials.</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>Protocol Title:</strong></p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n A Phase 2a, Multicenter, Open-label, Dose-finding, Dose escalation Study of Meplazumab in Adult Patients diagnosed with Uncomplicated <em>Plasmodium falciparum</em> Malaria.</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>Rationale</strong><strong>:</strong></p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Meplazumab, an erythrocytic stage-macromolecular antibody drug, has the potential to control clinical occurrence of falciparum malaria. Meplazumab is a humanized anti-CD147 immunoglobulin G subclass 2 (IgG2) monoclonal antibody with strong affinity to CD147. CD147 is expressed on erythrocyte lineage cells throughout erythroid development, including mature erythrocytes and is the target for Plasmodium merozoites to allow reorientation and subsequent invasion of the erythrocytes. Nonclinical studies have demonstrated that meplazumab binding to CD147 interferes with the receptor‑ligand interaction between CD147 and rhoptry-associated protein 2 (RAP2) of the <em>P. falciparum</em> merozoite and inhibits the formation of parasitophorous vacuoles of <em>P. falciparum</em> thus preventing the invasion of <em>P. falciparum</em> into human erythrocytes. Furthermore, the therapeutic and prophylactic effects of meplazumab were demonstrated in vivo using a human erythrocyte chimeric NOG mouse model, which is considered as an optimal choice for in vivo inhibition efficacy study for human-hosted <em>P. falciparum</em>.</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Meplazumab has previously been studied in healthy participants in two Phase 1 studies and has also been evaluated for activity in 2 completed clinical trials in patients diagnosed with coronavirus disease 2019 (COVID‑19). In the safety, tolerability, and pharmacokinetics study in healthy participants, MPZ‑I-01, results demonstrated a high and prolonged receptor occupancy (RO%) of meplazumab at CD147.</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n This Phase 2a study is designed as a dose escalation trial to assess safety of meplazumab in the target population and to evaluate whether meplazumab is efficacious in treating malaria. The data obtained in this study will be used to determine a recommended meplazumab dose for future Phase 2b and 3 efficacy trials.</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>Objectives and Endpoints</strong><strong>:</strong></p>\n<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" style=\"max-width: 100%; border-collapse: collapse; border-spacing: 0px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\" title=\"Synopsis\">\n <thead>\n <tr>\n <th style=\"padding: 4px 5px; line-height: 20px; text-align: left; vertical-align: bottom; border-top: 0px; width: 264px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>Objectives</strong></p>\n </th>\n <th style=\"padding: 4px 5px; line-height: 20px; text-align: left; vertical-align: bottom; border-top: 0px; width: 342px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>Endpoints</strong></p>\n </th>\n </tr>\n </thead>\n <tbody>\n <tr>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 606px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>Primary</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 264px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To evaluate the safety of meplazumab in an adult population with uncomplicated, symptomatic <em>P. falciparum</em> infection</li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Incidence and severity of AE</li>\n <li style=\"line-height: 20px;\">\n Incidence of (number of participants with):\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 0px 25px;\">\n <li style=\"line-height: 20px;\">\n Drug-related SAE</li>\n <li style=\"line-height: 20px;\">\n All-cause SAE</li>\n <li style=\"line-height: 20px;\">\n Drug-related AESI</li>\n <li style=\"line-height: 20px;\">\n All-cause AESI</li>\n <li style=\"line-height: 20px;\">\n Participants discontinuation/ withdrawals due to AE</li>\n </ul>\n </li>\n </ul>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 606px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>Secondary</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 264px; height: 50px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To evaluate the efficacy of meplazumab as defined by:\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 0px 25px;\">\n <li style=\"line-height: 20px;\">\n Early treatment failure</li>\n <li style=\"line-height: 20px;\">\n Late clinical failure</li>\n <li style=\"line-height: 20px;\">\n Late parasitological failure</li>\n <li style=\"line-height: 20px;\">\n Uncorrected ACPR</li>\n </ul>\n </li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px; height: 50px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Incidence (number of participants with) of early treatment failure</li>\n <li style=\"line-height: 20px;\">\n Incidence of late clinical failure</li>\n <li style=\"line-height: 20px;\">\n Incidence of late parasitological failure</li>\n <li style=\"line-height: 20px;\">\n Incidence of uncorrected ACPR at Day 28</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 264px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To evaluate PRR</li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n PRR at 72h</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 264px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To determine the recrudescence (see Section 9.3.7) and re-infection (see Section 9.3.7)</li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Incidence of (number of participants with) recrudescence and re-infection at Week 4</li>\n <li style=\"line-height: 20px;\">\n Time to recrudescence and re-infection at Week 4</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 264px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To determine the time to relief of fever</li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n FCT at 72h</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 264px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To determine the dose-response trend relationship between 3 dose  levels of meplazumab by evaluation of safety, efficacy and ACPR outcomes</li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Dose-response trend relationship between the 3 dose levels of meplazumab, based on change from baseline in the summary of the safety and efficacy outcomes to Week 4</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 264px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To evaluate the pharmacokinetics of meplazumab in serum</li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Meplazumab serum concentration-time profiles and PK parameters including but not limited to C<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">max</span>, t<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">max</span>, AUC<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">(0-last)</span>, AUC<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">(0-inf)</span>, t<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">½</span>, CL, V<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">z</span>, and V<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">ss</span></li>\n </ul>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 264px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To evaluate immunogenicity following meplazumab administration</li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Frequency of confirmed anti-drug antibody (ADA) response, ADA titers, and neutralizing activity</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 606px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>Exploratory</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 264px; height: 45px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To evaluate the efficacy of meplazumab by PCR-corrected ACPR</li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px; height: 45px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Incidence of (number of participants with) PCR‑corrected ACPR at Week 4</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 264px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To evaluate RO (%) of meplazumab in red blood cells following single dose administration</li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Meplazumab RO%-time profiles, pharmacodynamic parameters determined for RO including but not limited to maximum RO% and duration RO% (RO% half-life)</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 264px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To quantify the levels of complement regulatory proteins, the deposition of complement on  erythrocytes, and serum complement activation in human subjects treated with meplazumab.</li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Cell-surface expression of complement regulatory proteins and presence of complement products measured by flow cytometry; and complement activation measured by ELISA kit</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 264px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To evaluate the relationship between exposure to meplazumab and key efficacy and/or safety parameters</li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Graphical (and statistical, if appropriate) display of exposure versus response</li>\n </ul>\n </td>\n </tr>\n </tbody>\n</table>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Abbreviations: ACPR=adequate clinical & parasitological response; ADA=anti-drug antibodies; AE=adverse event; AESI =adverse event of special interest; AUC<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">(0‑inf)</span>=area under the concentration‑time curve extrapolated to infinity; AUC<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">(0‑last)</span>=area under the concentration‑time curve to the last quantifiable concentration; CL=systemic clearance; C<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">max</span>=maximum concentration; FCT=fever clearance time; polymerase chain reaction PCR=polymerase chain reaction; <em>P. falciparum</em>=<em>Plasmodium falciparum</em>; PRR=parasite reduction rate; RO=receptor occupancy; SAE=serious adverse event; t<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">½</span>=elimination half‑life; t<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">max</span>=time to C<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">max</span>; V<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">z</span>=volume of distribution; V<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">ss</span>=volume at steady state.</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>Overall Design:</strong></p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n This is a Phase 2a multicenter, open-label, dose-finding, dose escalation study. The study will recruit participants with confirmed <em>P. falciparum</em> infection. Up to 60 participants will be enrolled into 1 of 3 meplazumab dose levels (20 participants /dose level).</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>Number of Participants:</strong></p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Up to 60 participants will be enrolled into 1 of 3 meplazumab dose levels (20 participants/dose level).</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>Intervention Groups and Duration</strong><strong>:</strong></p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Participants will be administered a single intravenous (IV) infusion dose of meplazumab 120±5 minutes on Day 0 and hospitalized for 72 hours after dosing (up to Day 3) to monitor for safety and tolerability of therapy, and to ensure treatment response. During hospitalization, blood sampling for safety, pharmacokinetic (PK), and RO pharmacodynamic (PD) testing at predefined times will be collected as specified per the Schedule of Assessment (SoA). Furthermore, in a subset of first 10 participants/dose level, additional (serial) PK and PD samples will be collected at 1, 2, 4 and 8 hours post end-of-infusion. Up to 3 additional samples may be added to the Day 0-3 serial sample collection period.</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n If clinically well, participants may be discharged from the clinical unit on Day 3 at the Investigator’s discretion. Participants will return to the study center for follow-up visits on Days 28±2, 56±7, 84±7 and 182±7 (End of Study) for safety, tolerability, PK, PD (RO rate), and immunogenicity assessments as per the SoA (Weeks 4, 8, 12 and 26).</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>Data Monitoring/Other Committee: </strong>Yes</p>\n
      • study_title<div>\n A Phase 2a, Multicenter, Open-label, Dose-finding, Dose Escalation Study of Meplazumab in Adult Patients Diagnosed with</div>\n<div>\n Uncomplicated <em>Plasmodium falciparum</em> Malaria</div>\n<div>\n  </div>\n
      • laymans_summary<p>\n <span style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">Open-Label Study to evaluate the safety of meplazumab in an adult population with uncomplicated, symptomatic P. falciparum infection. Malaria is caused by Plasmodium, a parasite which is transmitted to humans by infected female anopheles mosquitoes (malaria vector). When infected anopheles bites a human, Plasmodium sporozoites in the mosquito’s saliva enter the bloodstream and migrate to the liver, followed by the merozoites reproduction within the hepatocytes. This stage is known as exoerythrocytic phase. Merozoites reproduce and form schizonts, which contain several thousands of merozoites. After the schizonts mature and rupture, merozoites are released into the blood and invade erythrocytes, hence initiating the merozoites reproduction in the erythrocytic phase. Current methods toward malaria elimination usually involve the combination of prevention and treatment. Artemisinin-based combination therapies (ACTs) are currently recommended by the World Health Organization for the treatment of malaria. Antimalarial drugs mainly include drugs to eliminate Plasmodium during the erythrocytic or exoerythrocytic phase. From the 1950s, falciparum malaria has developed general resistance to antimalarial drugs such as chloroquine, and sulfadoxine-pyrimethamine, leading to ineffective malaria control. Plasmodium developed higher resistance to the drugs used in combination in ACTs. Therefore, new antimalarial therapies and drugs are imperative due to the recurrent drug resistance of Plasmodium. Meplazumab, an erythrocytic stage-macromolecular antibody drug, has the potential to control clinical occurrence of falciparum malaria. Meplazumab is a humanized anti-CD147 immunoglobulin G subclass 2 (IgG2) monoclonal antibody with strong affinity to CD147. CD147 is expressed on erythrocyte lineage cells throughout erythroid development, including mature erythrocytes and is the target for Plasmodium merozoites to allow reorientation and subsequent invasion of the erythrocytes.</span></p>\n
      • short_titleMPZ-MAL-01
      • protocol_noECCT/24/02/03
      • version_noAmendment 1
      • date_of_protocol27-07-2023
      • study_drugMeplazumab
      • disease_conditionUncomplicated Plasmodium falciparum Malaria
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals1
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressamina.salim@iqvia.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantEsther M\'Openda
      • declaration_date106-02-2024
      • declaration_principal_investigatorProf. Videlis Nduba
      • declaration_date206-02-2024
      • placebo_presentNo
      • study_objectives<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" font-size:=\"\" style=\"max-width: 100%; border-collapse: collapse; border-spacing: 0px; color: rgb(51, 51, 51); font-family: \" title=\"Synopsis\" trebuchet=\"\">\n <thead>\n <tr>\n <th style=\"padding: 4px 5px; line-height: 20px; text-align: left; vertical-align: bottom; border-top: 0px; width: 264px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>Objectives</strong></p>\n </th>\n <th style=\"padding: 4px 5px; line-height: 20px; text-align: left; vertical-align: bottom; border-top: 0px; width: 342px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>Endpoints</strong></p>\n </th>\n </tr>\n </thead>\n <tbody>\n <tr>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 606px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>Primary</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 264px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To evaluate the safety of meplazumab in an adult population with uncomplicated, symptomatic <em>P. falciparum</em> infection</li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Incidence and severity of AE</li>\n <li style=\"line-height: 20px;\">\n Incidence of (number of participants with):\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 0px 25px;\">\n <li style=\"line-height: 20px;\">\n Drug-related SAE</li>\n <li style=\"line-height: 20px;\">\n All-cause SAE</li>\n <li style=\"line-height: 20px;\">\n Drug-related AESI</li>\n <li style=\"line-height: 20px;\">\n All-cause AESI</li>\n <li style=\"line-height: 20px;\">\n Participants discontinuation/ withdrawals due to AE</li>\n </ul>\n </li>\n </ul>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 606px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>Secondary</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 264px; height: 50px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To evaluate the efficacy of meplazumab as defined by\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 0px 25px;\">\n <li style=\"line-height: 20px;\">\n Early treatment failure</li>\n <li style=\"line-height: 20px;\">\n Late clinical failure</li>\n <li style=\"line-height: 20px;\">\n Late parasitological failure</li>\n <li style=\"line-height: 20px;\">\n Uncorrected ACPR</li>\n </ul>\n </li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px; height: 50px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Incidence (number of participants with) of early treatment failure</li>\n <li style=\"line-height: 20px;\">\n Incidence of late clinical failure</li>\n <li style=\"line-height: 20px;\">\n Incidence of late parasitological failure</li>\n <li style=\"line-height: 20px;\">\n Incidence of uncorrected ACPR at Day 28</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 264px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To evaluate PRR</li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n PRR at 72h</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 264px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To determine the recrudescence (see Section 9.3.7) and re-infection (see Section 9.3.7)</li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Incidence of (number of participants with) recrudescence and re-infection at Week 4</li>\n <li style=\"line-height: 20px;\">\n Time to recrudescence and re-infection at Week 4</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 264px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To determine the time to relief of fever</li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n FCT at 72h</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 264px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To determine the dose-response trend relationship between 3 dose levels of meplazumab by evaluation of safety, efficacy and ACPR outcomes</li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Dose-response trend relationship between the 3 dose levels of meplazumab, based on change from baseline in the summary of the safety and efficacy outcomes to Week 4</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 264px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To evaluate the pharmacokinetics of meplazumab in serum</li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Meplazumab serum concentration-time profiles and PK parameters including but not limited to C<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">max</span>, t<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">max</span>, AUC<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">(0-last)</span>, AUC<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">(0-inf)</span>, t<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">½</span>, CL, V<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">z</span>, and V<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">ss</span></li>\n </ul>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 264px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To evaluate immunogenicity following meplazumab administration</li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Frequency of confirmed ADA response, ADA titers, and neutralizing activity</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 606px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>Exploratory</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 264px; height: 45px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To evaluate the efficacy of meplazumab by PCR-corrected ACPR</li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px; height: 45px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Incidence of (number of participants with) PCR‑corrected ACPR at Week 4</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 264px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To evaluate RO (%) of meplazumab in red blood cells following single dose administration</li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Meplazumab RO%-time profiles, pharmacodynamic parameters determined for RO including but not limited to maximum RO% and duration RO% (RO% half-life)</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 264px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To quantify the levels of complement regulatory proteins, the deposition of complement on  erythrocytes, and serum complement activation in human subjects treated with meplazumab.</li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Cell-surface expression of complement regulatory proteins and presence of complement products measured by flow cytometry; and complement activation measured by ELISA kit</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 264px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To evaluate the relationship between exposure to meplazumab and key efficacy and/or safety parameters</li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Graphical (and statistical, if appropriate) display of exposure versus response</li>\n </ul>\n </td>\n </tr>\n </tbody>\n</table>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Abbreviations: ACPR=adequate clinical & parasitological response; ADA=anti-drug antibodies; AE=adverse event; AESI=adverse event of special interest; AUC<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">(0‑inf)</span>=area under the concentration‑time curve extrapolated to infinity; AUC<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">(0‑last)</span>=area under the concentration‑time curve to the last quantifiable concentration; CL=systemic clearance; C<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">max</span>=maximum concentration; FCT=fever clearance time; polymerase chain reaction PCR=polymerase chain reaction; <em>P. falciparum</em>=<em>Plasmodium falciparum</em>; PRR=parasite reduction rate; RO=receptor occupancy; SAE=serious adverse event; t<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">½</span>=elimination half‑life; t<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">max</span>=time to C<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">max</span>; V<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">z</span>=volume of distribution; V<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">ss</span>=volume at steady state.</p>\n
      • principal_inclusion_criteria<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Participants are eligible to be included in the study only if all of the following criteria apply:</p>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n Ability to provide informed consent signed by the study participant or legally authorized representative</li>\n <li style=\"line-height: 20px;\">\n Adults 18 to 55 years at the time of signing the informed consent form (ICF)</li>\n <li style=\"line-height: 20px;\">\n Female participants are eligible to participate if they do not qualify as a woman of childbearing potential (WOCBP), as defined in Section 10.4.</li>\n <li style=\"line-height: 20px;\">\n Male participants who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception as described in Section 10.4.</li>\n <li style=\"line-height: 20px;\">\n BMI ≥18 to ≤30 kg/m<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; top: -0.5em;\">2</span></li>\n <li style=\"line-height: 20px;\">\n Mono-infection with <em>P. falciparum</em> documented by:</li>\n</ol>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n Microscopically confirmed parasite infection using Giemsa-stained thick film (refer to the laboratory manual for details) consisting of 1000 – 100,000 asexual parasites /µL of blood <strong><u>and</u></strong></li>\n <li style=\"line-height: 20px;\">\n Documented fever (≥38.0°C oral, rectal or tympanic; ≥37.5°C axillary) or documented history of fever in previous 24 hours</li>\n</ul>\n
      • principal_exclusion_criteria<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Participants are NOT eligible to be included in the study if any of the following exclusion criteria apply:</p>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n Presence of severe malaria (as defined by World Health Organization Guidelines for Malaria 16 February 2021).</li>\n</ol>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n Severe falciparum malaria is defined as one or more of the following, occurring in the absence of an identified alternative cause and in the presence of <em>P. falciparum</em> asexual parasitemia.\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 0px 25px;\">\n <li style=\"line-height: 20px;\">\n Impaired consciousness: A Glasgow coma score <11 in adults</li>\n <li style=\"line-height: 20px;\">\n Prostration: Generalized weakness so that the person is unable to sit, stand or walk without assistance</li>\n <li style=\"line-height: 20px;\">\n Multiple convulsions: More than 2 episodes within 24 h</li>\n <li style=\"line-height: 20px;\">\n Acidosis: A base deficit of >8 mEq/L or, if not available, a plasma bicarbonate level of <15 mmol/L or venous plasma lactate ≥5 mmol/L. Severe acidosis manifests clinically as respiratory distress (rapid, deep, labored breathing).</li>\n <li style=\"line-height: 20px;\">\n Hypoglycemia: Blood or plasma glucose <2.2 mmol/L (<40 mg/dL)</li>\n <li style=\"line-height: 20px;\">\n Severe malarial anemia: Hemoglobin concentration ≤7 g/dL or a hematocrit of ≤20% in adults with a parasite count >10,000/μL</li>\n <li style=\"line-height: 20px;\">\n Renal impairment: Plasma or serum creatinine >265 μmol/L (3 mg/dL) or blood urea >20 mmol/L</li>\n <li style=\"line-height: 20px;\">\n Jaundice: Plasma or serum bilirubin >50 μmol/L (3 mg/dL) with a parasite count >100,000/ μL</li>\n <li style=\"line-height: 20px;\">\n Pulmonary edema: Radiologically confirmed or oxygen saturation <92% on room air with a respiratory rate >30/min, often with chest indrawing and crepitations on auscultation</li>\n <li style=\"line-height: 20px;\">\n Significant bleeding: Including recurrent or prolonged bleeding from the nose, gums or venepuncture sites; hematemesis or melena</li>\n <li style=\"line-height: 20px;\">\n Shock: Compensated shock is defined as capillary refill ≥3 s or temperature gradient on leg (mid to proximal limb), but no hypotension. Decompensated shock is defined as systolic blood pressure <80 mmHg in adults, with evidence of impaired perfusion (cool peripheries or prolonged capillary refill).</li>\n <li style=\"line-height: 20px;\">\n Hyperparasitemia: <em>P. falciparum</em> parasitemia >10%</li>\n </ul>\n </li>\n</ul>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"2\">\n Antimalarial treatment (alone or in combination) during the following periods before Screening:</li>\n</ol>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n Piperaquine, mefloquine, naphthoquine or sulfadoxine-pyrimethamine within 6 weeks prior to Screening.</li>\n <li style=\"line-height: 20px;\">\n Amodiaquine, chloroquine within 4 weeks prior to Screening.</li>\n <li style=\"line-height: 20px;\">\n Any artemisinin derivative (artesunate, artemether or dihydroartemisinin), quinine, lumefantrine or any other antimalarial treatment or antibiotic with antimalarial activity (including cotrimoxazole, tetracyclines, quinolones and fluoroquinolones and azithromycin) within 14 days prior to Screening.</li>\n <li style=\"line-height: 20px;\">\n Any herbal products or traditional medicines, within the past 7 days.</li>\n</ul>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"3\">\n Previous participation in any malaria vaccine study or received malaria vaccine within 3 months of Screening Visit.</li>\n <li style=\"line-height: 20px;\" value=\"4\">\n Known allergy to any study medication, including allergy to any component of protocol prescribed rescue treatment i.e., country-specific ACT regimen.</li>\n <li style=\"line-height: 20px;\" value=\"5\">\n Any clinically important illness as judged by the investigator, including but not limited to a history of clinically significant chronic respiratory disease (eg, chronic obstructive pulmonary disease [COPD] or asthma), medical/surgical procedure, or trauma within 4 weeks of the first administration of investigational product.</li>\n <li style=\"line-height: 20px;\" value=\"6\">\n Participants participate in another clinical study. There will be a need for washout with 5 half-lives depending on the study treatment or 30 days, whichever is longer.</li>\n <li style=\"line-height: 20px;\" value=\"7\">\n Use of anti-cancer, anti-transplant rejection, or immunomodulatory biological drug or kinase inhibitor (e.g., tocilizumab, sarilumab) or Janus kinase inhibitors (within 30 days of enrollment or 5 times the half-life [whichever is longer]).</li>\n <li style=\"line-height: 20px;\" value=\"8\">\n  Systemic administration of corticosteroids (PO/IV/IM) at a dose of ≥20 mg/day of prednisone or equivalent for more than 14 consecutive days within 90 days prior to informed consent. Topical, inhaled, and intranasal corticosteroids are permitted. Intermittent use (one dose in 30 days) of intra-articular corticosteroids are also permitted.</li>\n <li style=\"line-height: 20px;\" value=\"9\">\n Live (live-attenuated) vaccines are not permitted within 2 weeks prior to study treatment or during the study treatment and safety follow-up periods.</li>\n <li style=\"line-height: 20px;\" value=\"10\">\n Presence of Hepatitis A IgM, Hepatitis B surface antigen, or Hepatitis C antibody, or Anti-HIV1 and/or HIV2 antibody , or Rapid Plasma Reagin test positive for syphilis..</li>\n <li style=\"line-height: 20px;\" value=\"11\">\n TBL >1.5 × ULN, ALT >2 × ULN, or AST >2 × ULN.</li>\n <li style=\"line-height: 20px;\" value=\"12\">\n Hematocrit <20%, hemoglobin <70 g/L (<7 g/dL), or white blood count >15,000/μL.</li>\n <li style=\"line-height: 20px;\" value=\"13\">\n Creatinine >1.5 × ULN.</li>\n</ol>\n
      • primary_end_points<p font-size:=\"\" style=\"margin: 0px 0px 10px 18pt; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n ·       Incidence and severity of AE</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px 18pt; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n ·       Incidence of (number of participants with):</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px 54pt; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n o   Drug-related SAE</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px 54pt; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n o   All-cause SAE</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px 54pt; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n o   Drug-related AESI</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px 54pt; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n o   All-cause AESI</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px 54pt; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n o  Participants discontinuation/ withdrawals due to AE</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response1
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory1
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledNo
      • site_capacity(null)
      • staff_numbers<p>\n <strong><em><u>KEMRI: Siaya Clinical Research Annexe</u></em></strong></p>\n<p>\n <strong><em><u>Study Site </u></em></strong></p>\n<p>\n The study will be conducted at the KEMRI CRDR Clinical Research Annexe Siaya  within Siaya County Referral Hospital. KEMRI has a modern research annex at the Siaya County Referral hospital with capacity to conduct phase I to Phase IV studies through training and experience.</p>\n<p>\n The site has conducted more than 20 clinical trials since establishment. The site is ICH/GCP compliant with all staff undertaking the GCP and ethics training prior to conducting the delegated duties. The clinical research team is well trained and experienced in data collection including eligibility assessment and participant care during follow up.</p>\n<p>\n The site lab is well equipped with the necessary equipment and capacity to collect, process, store and manage the collected study samples. The equipments are well maintained with regular calibration. The site laboratory staff are qualified by education, training and experience. In addition, they are GCLP and Laboratory IATA trained and Certified.</p>\n<p>\n The Site pharmacy is equipped with fridges and temperature monitoring devices for IP management.</p>\n<p>\n In addition, the community team is GPP compliant with good recruitment and retention plan that is goal oriented.</p>\n<p>\n <strong><u>Staffs</u></strong></p>\n<p>\n Site investigators responsible for day to day running of the project include:</p>\n<p>\n Principal Investigator(1) Prof. Videlis Nduba- who will be responsible for the overall conduct of the trial at this study site, administrative actions between site, Institutional Review Boards, and the sponsor, oversight of site activities and clinical care provision to study participants. He will contribute to the writing of the scientific report.</p>\n<p>\n Medical Officers(2) Dr Mercy Mwale and Dr. Mike Odoyo- who will be responsible for the clinical conduct of the trial, the care provided to patients, oversight of study activities at the site. Reviewing potential Study participants for eligibility, supervising Clinical Officers, review of laboratory results, adverse events and serious adverse events surveillance, documentation and reporting, providing first hand clinical care to participants. Data entry,</p>\n<p>\n Pharmacists(2) Dr. Ian Mwangi and Dr. Emily Naiserrian- who will be responsible for the application of import license for Investigational Products, IMP accountability from receipt to storage, cold chain maintenance, preparation and dispensing and accountability logs, and IMP destruction.</p>\n<p>\n 2 Pharmaceutical technologists, 6 Nurses, 6 Quality Assurance/Quality Control Officers, 4 Clinical Officers, 8 Community Interviewers, 4 Data personnel and 6 Laboratory Personnel to conduct the clinical trials and offer medical care to research participants.</p>\n<p>\n  </p>\n
      • other_details_explanation<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">No</span></p>\n
      • other_details_regulatory_notapproved<div>\n Rwanda Food and Drug Authority- submission 3 November 2023, approval pending</div>\n<div>\n Ghana Food and Drug Authority- submission 17 October 2023, approval pending</div>\n
      • other_details_regulatory_approved<p>\n Kenya Pharmacy and Poisons Board (KPPB) - Dr Ogutu - ECCT/23/11/06</p>\n
      • other_details_regulatory_rejected<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">Not Applicable</span></p>\n
      • other_details_regulatory_halted<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">Not Applicable</span></p>\n
      • estimated_duration2 years
      • design_controlled_randomised
      • design_controlled_open
      • design_controlled_single_blind
      • design_controlled_double_blind
      • design_controlled_parallel_group
      • design_controlled_cross_over
      • design_controlled_other
      • design_controlled_specify
      • design_controlled_comparator
      • design_controlled_other_medicinal
      • design_controlled_placebo
      • design_controlled_medicinal_other
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states4
      • number_of_sites3
      • multi_country_listRwanda \nGhana \nGabon
      • data_monitoring_committeeYes
      • total_enrolment_per_siteRecruitment is competitive between sites and countries. There are no minimum or maximum number per site.
      • total_participants_worldwide60
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsNo
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameBernhards
      • investigator1_middle_name
      • investigator1_family_nameOgutu
      • investigator1_qualificationMedical Doctor
      • investigator1_professional_addressAHERO CLINICAL TRIALS UNIT, Ahero County Hospital, Nairobi, Kenya
      • investigator1_telephone+254733812613
      • investigator1_emailOgutu6@gmail.com
      • organisations_transferred_Yes
      • number_participants9 participants
      • notification
      • approval_date08-03-2024
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted06-02-2024
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReveiwer comments for Prof. Kokwaro and Dr. Kosgei addressed comprehensively.
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2024-10-08 12:57:28
      • created2023-11-27 09:12:39
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id1012
        • application_id1352
        • given_nameVidelis
        • middle_name
        • family_nameNduba
        • qualificationMedical Doctor
        • professional_addressKEMRI Clinical Research Annex, Within Siaya County Referral Hospital Ground. P.O BOX 144-40600 ,Siaya, Kenya
        • telephone+254724522474
        • emailvnduba@gmail.com
        • created2023-11-27 09:22:29
        • modified2024-02-06 14:57:46
    • SiteDetail(array)
      • 0(array)
        • id1637
        • application_id1352
        • county_id41
        • site_nameKenya Medical Research Institute(KEMRI):Siaya Clinical Research Annex
        • physical_addressKEMRI Clinical Research Annex, Within Siaya County Referral Hospital Ground. P.O BOX 144-40600 ,Siaya, Kenya
        • contact_details+254724522474
        • contact_personProf Videlis Nduba
        • site_capacity(null)
        • misc(null)
        • created2023-11-27 09:22:29
        • modified2024-02-06 14:57:46
        • County(array)
          • id41
          • county_nameSiaya
          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
      • 1(array)
        • id1638
        • application_id1352
        • county_id42
        • site_nameVictoria Biomedical Research Institute (VIBRI)
        • physical_addressKisumu County Referral Hospital, off Ang’awa Avenue, P O Box 7180-40100, Kisumu, Kenya
        • contact_details+254 720 597654
        • contact_personDr Lucas Otieno Tina
        • site_capacity(null)
        • misc(null)
        • created2023-11-27 10:30:37
        • modified2024-02-06 14:57:46
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 2(array)
        • id1639
        • application_id1352
        • county_id42
        • site_nameAHERO CLINICAL TRIALS UNIT
        • physical_addressHOUSED WITHIN AHERO COUNTY HOSPITAL, PO BOX 54,40100 KISUMU, ALONG KISUMU NAIROBI HIGHWAY FIELD SITE FOR CENTRE FOR RESEARCH IN THERAPEUATIC SCIENCES
        • contact_details+254733812613
        • contact_personDr. Bernhards Ogutu
        • site_capacity(null)
        • misc(null)
        • created2023-11-27 10:30:37
        • modified2024-02-06 14:57:46
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
    • Sponsor(array)
      • 0(array)
        • id711
        • application_id1352
        • sponsorJiangsu Pacific Meinuoke Biopharmaceutical Co. Ltd.(PMBP)
        • sponsor_typeIndustry
        • contact_personXiaochun Chen
        • addressNo. 128 Hehai West Road, Xinbei District, Changzhou, 213022, Jiangsu People’s Republic of China
        • telephone_number+86 15851999825
        • fax_number
        • cell_number0519-6888988
        • email_addresscxc@pmbp.cn
        • created2023-11-27 09:22:29
        • modified2024-02-06 14:57:46
• page_options(array)
  • 55
  • 1010
• redir
• $request->data(array)
  • Application(array)
    • trial_therapeutic_exploratory1
• $this->validationErrors(array)
  • Permission(empty)
  • Aro(empty)
  • Aco(empty)
  • Application(empty)
  • User(empty)
  • TrialStatus(empty)
  • InvestigatorContact(empty)
  • Sponsor(empty)
  • SiteDetail(empty)
  • County(empty)
• Loaded Helpers(array)
  • 0Html
  • 1Form
  • 2Session
  • 3Text
  • 4Number
  • 5SimpleGraph
  • 6Paginator
  • 7DebugTimer
  • 8Toolbar
  • 9HtmlToolbar

App Constants

CakePHP Constants

PHP Environment

Included Files

Include Paths

• 0/var/www/html/ctr/app/Plugin/Media/Lib/mm/src
• 1/var/www/html/ctr/lib
• 3/usr/share/php
• 4/usr/share/pear
• 5-> /var/www/html/ctr/lib/Cake/

Included Files

• core(array)
  • Behavior(array)
    • 0CORE/Model/Behavior/TreeBehavior.php
    • 1CORE/Model/Behavior/ContainableBehavior.php
    • 2CORE/Model/Behavior/AclBehavior.php
  • Cache(array)
    • 0CORE/Cache/Cache.php
    • 1CORE/Cache/Engine/FileEngine.php
    • 2CORE/Cache/CacheEngine.php
  • Component(array)
    • 0CORE/Controller/Component/AclComponent.php
    • 1CORE/Controller/Component/Acl/DbAcl.php
    • 2CORE/Controller/Component/Acl/AclInterface.php
    • 3CORE/Controller/Component/AuthComponent.php
    • 4CORE/Controller/Component/RequestHandlerComponent.php
    • 5CORE/Controller/Component/SessionComponent.php
    • 6CORE/Controller/Component/PaginatorComponent.php
  • Config(array)
    • 0CORE/Config/routes.php
    • 1CORE/Config/config.php
  • Controller(array)
    • 0CORE/Controller/Controller.php
    • 1CORE/Controller/ComponentCollection.php
    • 2CORE/Controller/Component.php
  • Datasource(array)
    • 0CORE/Model/Datasource/CakeSession.php
    • 1CORE/Model/Datasource/Database/Mysql.php
    • 2CORE/Model/Datasource/DboSource.php
    • 3CORE/Model/Datasource/DataSource.php
  • Error(array)
    • 0CORE/Error/exceptions.php
    • 1CORE/Error/ErrorHandler.php
  • I18n(array)
    • 0CORE/I18n/I18n.php
    • 1CORE/I18n/L10n.php
  • Log(array)
    • 0CORE/Log/CakeLog.php
    • 1CORE/Log/LogEngineCollection.php
    • 2CORE/Log/Engine/FileLog.php
    • 3CORE/Log/Engine/BaseLog.php
    • 4CORE/Log/CakeLogInterface.php
  • Model(array)
    • 0CORE/Model/ConnectionManager.php
    • 1CORE/Model/Permission.php
    • 2CORE/Model/Model.php
    • 3CORE/Model/BehaviorCollection.php
    • 4CORE/Model/Aro.php
    • 5CORE/Model/AclNode.php
    • 6CORE/Model/Aco.php
    • 7CORE/Model/ModelBehavior.php
  • Network(array)
    • 0CORE/Network/CakeRequest.php
    • 1CORE/Network/CakeResponse.php
  • Other(array)
    • 0CORE/bootstrap.php
    • 1CORE/basics.php
    • 2CORE/Core/App.php
    • 3CORE/Core/Configure.php
    • 4CORE/Core/CakePlugin.php
    • 5CORE/Event/CakeEventListener.php
    • 6CORE/Event/CakeEvent.php
    • 7CORE/Event/CakeEventManager.php
    • 8CORE/Core/Object.php
  • Routing(array)
    • 0CORE/Routing/Dispatcher.php
    • 1CORE/Routing/Filter/AssetDispatcher.php
    • 2CORE/Routing/DispatcherFilter.php
    • 3CORE/Routing/Filter/CacheDispatcher.php
    • 4CORE/Routing/Router.php
    • 5CORE/Routing/Route/CakeRoute.php
    • 6CORE/Routing/Route/PluginShortRoute.php
  • Utility(array)
    • 0CORE/Utility/Hash.php
    • 1CORE/Utility/Inflector.php
    • 2CORE/Utility/ObjectCollection.php
    • 3CORE/Utility/Debugger.php
    • 4CORE/Utility/String.php
    • 5CORE/Utility/ClassRegistry.php
    • 6CORE/Utility/Set.php
    • 7CORE/Utility/Sanitize.php
  • View(array)
    • 0CORE/View/HelperCollection.php
• app(array)
  • Behavior(array)
    • 0APP/Model/Behavior/SoftDeleteBehavior.php
  • Config(array)
    • 0APP/Config/core.php
    • 1APP/Config/bootstrap.php
    • 2APP/Config/routes.php
    • 3APP/Config/database.php
  • Controller(array)
    • 0APP/Controller/ApplicationsController.php
    • 1APP/Controller/AppController.php
  • Model(array)
    • 0APP/Model/AppModel.php
    • 1APP/Model/Application.php
    • 2APP/Model/User.php
    • 3APP/Model/TrialStatus.php
    • 4APP/Model/InvestigatorContact.php
    • 5APP/Model/Sponsor.php
    • 6APP/Model/SiteDetail.php
    • 7APP/Model/County.php
  • Other(array)
    • 0APP/webroot/index.php
• plugins(array)
  • CakePdf(array)
    • Config(array)
      • 0CakePdf/Config/bootstrap.php
      • 1CakePdf/Config/routes.php
  • CakeResque(array)
    • Config(array)
      • 0CakeResque/Config/bootstrap.php
    • Plugin(array)
      • 0CakeResque/Lib/CakeResque.php
      • 1CakeResque/vendor/kamisama/php-resque-ex/lib/Resque.php
      • 2CakeResque/vendor/kamisama/php-resque-ex/lib/Resque/Event.php
      • 3CakeResque/vendor/kamisama/php-resque-ex/lib/Resque/Exception.php
  • DebugKit(array)
    • Component(array)
      • 0DebugKit/Controller/Component/ToolbarComponent.php
    • Plugin(array)
      • 0DebugKit/Lib/DebugMemory.php
      • 1DebugKit/Lib/Panel/HistoryPanel.php
      • 2DebugKit/Lib/DebugPanel.php
      • 3DebugKit/Lib/Panel/SessionPanel.php
      • 4DebugKit/Lib/Panel/RequestPanel.php
      • 5DebugKit/Lib/Panel/SqlLogPanel.php
      • 6DebugKit/Lib/Panel/TimerPanel.php
      • 7DebugKit/Lib/Panel/LogPanel.php
      • 8DebugKit/Lib/Log/Engine/DebugKitLog.php
      • 9DebugKit/Lib/Panel/VariablesPanel.php
      • 10DebugKit/Lib/Panel/EnvironmentPanel.php
      • 11DebugKit/Lib/Panel/IncludePanel.php
      • 12DebugKit/Lib/DebugTimer.php
  • Media(array)
    • Config(array)
      • 0Media/Config/bootstrap.php
    • Plugin(array)
      • 0Media/Lib/mm/src/Mime/Type.php
      • 1Media/Lib/mm/src/Mime/Type/Magic/Adapter/Fileinfo.php
      • 2Media/Lib/mm/src/Mime/Type/Magic/Adapter.php
      • 3Media/Lib/mm/src/Mime/Type/Glob/Adapter/Memory.php
      • 4Media/Lib/mm/src/Mime/Type/Glob/Adapter.php
      • 5Media/Lib/mm/src/Media/Process.php
      • 6Media/Lib/mm/src/Media/Info.php
  • Search(array)
    • Component(array)
      • 0Search/Controller/Component/PrgComponent.php
    • Behavior(array)
      • 0Search/Model/Behavior/SearchableBehavior.php
  • Shim(array)
    • Config(array)
      • 0Shim/Config/bootstrap.php
  • Tools(array)
    • Config(array)
      • 0Tools/Config/bootstrap.php